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Research Article
 

Exposure to Gasoline Vapours: A Potential Risk Factor for Atherosclerosis in Male and Female Rats



F.E. Uboh, M.I. Akpanabiatu, I.J. Atangwho and Y. Alozie
 
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ABSTRACT

A gender-dependent potential atherosclerotic risk is reported in this study to be associated with exposure to gasoline vapours in rats model. The atherosclerotic risk was assessed from the serum lipid and some electrolytes (Na+, K+ and Cl¯) profiles in male and female rats exposed wholly to 17.8±2.6 cm3/h/kg/m3/day of gasoline vapours (8 h daily, 6 days week-1) for 20 weeks in exposure chambers. A significant increase (p<0.05) in serum total cholesterol (TC), triglycerides (TGs), Low Density Lipoprotein-Cholesterol (LDL-C), Very Low Density Lipoprotein-Cholesterol (VLDL-C), K+ and decrease (p<0.05) in High Density Lipoprotein-Cholesterol (HDL-C), Na+ and Cl- was obtained for both male and female rats exposed to gasoline vapours. These results showed a state of hyperkalaemia, hyponatraemia, increased TG/HDL-C ratio and Atherogenic Index of Plasma (AIP) in male and female rats exposed to gasoline vapours. However, the comparative percentage increase in serum TC, TGs, LDL-C, VLDL-C, K+, as well as percentage decrease in serum HDL-C, Na+ and Cl¯ reported to be associated with exposure to gasoline vapours, were observed to be significantly higher (p<0.05) in females than the male rats. Since hyperlipidaemia, hyperkalaemia and hyponatraemia are known to be implicated in atherosclerosis, the result of this study gives a clear indication that gasoline vapours is among the risk factors for atherosclerosis and that the females are more adversely affected than the males in rats model.

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  How to cite this article:

F.E. Uboh, M.I. Akpanabiatu, I.J. Atangwho and Y. Alozie, 2008. Exposure to Gasoline Vapours: A Potential Risk Factor for Atherosclerosis in Male and Female Rats. Journal of Pharmacology and Toxicology, 3: 600-609.

DOI: 10.3923/jpt.2008.600.609

URL: https://scialert.net/abstract/?doi=jpt.2008.600.609
 

INTRODUCTION

Gasoline is one of the highly volatile products of petroleum fractionation. Evaporation of liquid gasoline generate gasoline vapours into the environments. These vapours are ubiquitous in the environment and constitute some components of petroleum pollutants in the atmosphere. A good percent of human populace is directly or indirectly exposed to these pollutants in the course of their day to day activities.

However, the commonest sites of exposure to these pollutants from gasoline vapours include refineries, oil fields, refueling stations, petrochemical and petrochemical-related industries as well as traffic-congested areas. Hence, the population at greater risk of frequent exposure includes those occupationally exposed, as well as those residing in traffic-congested areas. Reports indicate that chronically exposed individuals are the petroleum drillers, refinery and petrochemical workers, refuel station attendants and automobile mechanics (Carballo et al., 1995; Rabble and Wong, 1996).

Potential health hazards associated with chronic or sub-chronic exposure to these ubiquitous pollutants in the environment has been the concern of the general public and scientific community in particular. It has been reported that more saturated hydrocarbons than unsaturated aromatic hydrocarbons are detected in human and animal blood after inhalation exposure to equal concentration (Zahlsen et al., 1993). Both the saturated and unsaturated aromatic hydrocarbons form a proportion of gasoline constituents. Unleaded gasoline is reported to contain about 300 different hydrocarbon fraction most of which are very volatile. Some of these gasoline vapours’ constituents (including alkanes, benzenes, xylenes and tetraethyl lead) have been reported to be haematotoxic in humans and experimental animals (Azevedo et al., 1996; Rothman et al., 1996; Synder and Hedli, 1996). Also, our previous studies showed that inhalation and while body exposure of rats to gasoline vapours caused haematotoxicity (Uboh et al., 2007a), hepatotoxicity (Uboh et al., 2007b) and nephrotoxicity (Uboh et al., 2008) in the animal model. There is dearth of information on whether exposure to gasoline vapours may be risk factor to atherosclerosis or not.

Atherosclerosis and cardiovascular disease are known to be among the heading cause of deaths in the recent times (Gambhir et al., 2001). Atherosclerosis is known to be characterized by low level of High Density Lipoprotein-Cholesterol (HDL-C), high levels of total cholesterol (i.e., hyper cholesterolaemia), Low Density Lipoprotein Cholesterol (LDL-C) and triglycerides (TG) in the plasma (Warren and Halpert, 2004; Nasiruddin and Ahmad, 2006). Atherosclerotic condition however, may also be ascertained from such atherogenic index as the logarithm of the ratio of TG to HDL-C, i.e., Atherogenic Index of Plasma (AIP). While Gaziano et al. (1997) and Frohlich and Dobiáová (2003) reported that the ratio of TG to HDL-C is a strong predictor of atherosclerosis condition, hence myocardial infarction, Tan et al. (2004) and Dobiáová (2004) maintained that the logarithm of the ratio of TG to HDL-C in molar concentrations, i.e., log (TG/HDL), referred to as the Atherogenic Index of Plasma (AIP) is more sensitive. However, either AIP or TG/HDL-C may be used to evaluate the atherosclerotic state of a subject (Dobiáová and Frohlich, 2001), although Tan et al. (2004) in one of their studies reported the P values for AIP to be consistently lower than those for TG/HDL.

There are several risk factors that contribute to the development of atherosclerosis. While some of these factors can be controlled, some cannot be controlled. Among these factors is reported to include:

Documented atheroma in any artery
Diabetes or just upper normal blood glucose and insulin levels (Gilling et al., 2002)
Dyslipidermia (cholesterol and triglyceride level disturbances) having a high blood concentration of LDL (bad cholesterol) particles, VLDL particles and low concentration of functioning HDL (good cholesterol) particles (Gambhir et al., 2001; Rader, 2002; Nasiruddin and Ahmad, 2006)

Several internal chemical markers indicating ongoing inflammation may also relate to relative risk (Frohlich and Dobiáová, 2003).

These risk factors usually operate synergistically to promote earlier or later consequences of atherosclerosis.

MATERIALS AND METHODS

Animals and Animal Handling
Twenty eight Wistar albino rats weighing 180-200 g were obtained from the animal house of the Department of Biochemistry, University of Calabar, Calabar, Nigeria and used for this study, which lasted from March, 2009 to May, 2009. The animals were allowed one week of acclimatization to laboratory conditions and handling, after which they were distributed, according to weight into three groups as outlined below. The animals were housed individually in cages with plastic bottom and wire mesh top (North Kent Co. Ltd.) and fed with normal rat chow (Guinea Feeds Product) purchased from the High Quality Livestock Feeds stores, Calabar, Nigeria. They were supplied with tap water ad libitum throughout the experimental period. The control groups (Mc and Fc) were maintained in the gasoline vapours-free section of the animal room adequately ventilated under standard conditions (ambient temperature, 28±2°C and relative humidity, 46%, with a light/dark cycle of 12/12 h). The test groups (Mt and Ft) were kept in the exposure chambers (vapours cupboards) previously saturated respectively with Premium Motor Spirit (PMS) blend of gasoline vapours during the exposure periods. The liquid gasoline (PMS blend) was obtained from the Mobil Refueling station, Marian Road, Calabar, Nigeria.

All animal experiments were carried out in accordance with the guidelines of the Institutional Animal Ethics Committee.

Distribution of Experimental Group

Group No.of rats Treatment
Male control (Mc) 7 Vapours-free
Male test (Mt) 7 Exposed to gasoline vapour
Female control (Fc) 7 Vapours-Free
Female test (Ft) 7 Exposed to gasoline vapour

Exposure to Gasoline Vapours
The animals in the test groups were wholly exposed to 17.8 cm3/h/kg/m3 (target concentration) of vapourized Premium Motor Spirit (PMS) blend of unleaded gasoline (UG) vapours for 8 h day-1, 6 days week-1, for 20 weeks in a glass exposure chambers (1.5x0.9x2.1 m). Exposure conditions were chosen to reproduce those used in our previous studies (Uboh et al., 2007a, b, 2008). The exposures were routinely conducted from 9.00 am to 5.00 pm on week days, including holidays to mimic workplace exposure. The chamber design, exposure generation system and monitoring system were the same as those previously described (Uboh et al., 2007a, b, 2008), with chamber concentrations of the UG determined daily. The average daily chamber concentrations of UG during exposure periods were 17.8±2.6 cm3/h/kg/m3 (about 85.4% of target concentration). At the end of each day’s exposure period, the animals were transferred to gasoline vapours-free section of the experimental animal house and maintained under the same standard conditions as the animals in control groups until the next day. During the exposure period, the initial and final volumes of liquid gasoline were respectively recorded before and after daily exposure. The daily differences in volume were used to estimate the relative concentrations of vapours used in this exposure method.

Collection and Handling of Blood Serum for Analyses
Twenty-four hours after last exposure, the animals were anaesthetized with chloroform vapour and dissected. Whole blood from each animal was collected by cardiac puncture into well-labeled non-heparinized sample tubes and allowed to clot for 3 h in iced water. The serum was separated from the clots after centrifuging at 10,000 rpm for 5 min, using bench top centrifuge (MSE Minor, England), into well-labeled plain sample bottles and used for assays.

Biochemical Assays
Serum Lipid Profile
Kits obtained from the Randox Chemical Company, UK were used for lipid profile assays. The high performance enzymatic colorimetric, CHOD-PAP method described by Richmond (1973) was used to estimate total serum cholesterol. The principle is based on the proportionate formation of hydrogen peroxide (following oxidation of free cholesterol), which is quantified when treated with chromogem, 4-aminoantipyrine. A coloured compound whose intensity is in proportion to the evolved peroxide and thus total cholesterol concentration in the sample, is formed and assayed spectrophotometrically, using HAICH, DR3000, Germany model of spectrophotometer.

Serum triglycerides were estimated by the modified enzymatic colorimeric test, according to the Glycerol Phosphate Oxidase (GPO) method. It is based on the action of L-d-glycerol phosphate oxidase on glycerol-3-phosphate and glycerol, obtained from the lipase action on triglycerides in serum. Hydrogen peroxide, a by-product of the GPO reaction is estimated as already described for total cholesterol.

HDL-cholesterol estimation employed the method of Richmond (1973). The principle entails the separation of HDL-cholesterol from chylomicrons, VLDL-C and LDL-C with a suitable precipitant and then estimation of cholesterol by the method described for total serum cholesterol.

VLDL and LDL cholesterols were obtained by calculations using the empirical relationships of Friedwald et al. (1972).

AIP (Atherogenic Index of Plasma) was derived from the relationship described Dobiáová and Frohlich (2001).

Serum Electrolytes
Sodium and potassium ions (Na+ and K+) concentrations in serum were determined by Flame Photometric method of Vogel (1960), while chloride ion (Cl-) concentration in serum was determined by titration methods of AOAC (1990).

Statistical Analysis
All data are expressed as Mean±SEM. The mean values for the test groups were compared with the respective control group values for statistical difference using Student’s t-test. Differences between groups were considered significant at p<0.05.

RESULTS

The effects of gasoline vapours on the serum lipid profile and some electrolytes (Na+, K+ and Cl¯) concentrations are summarized in Table 1 and 2. The result showed that exposure to gasoline vapours caused a significant increase (p<0.05) in serum TC, TG, LDL-C, VLDL-C and K+, as well as a significant decrease (p<0.05) in the serum HDL-C, Na+ and Cl¯ concentrations in both male and female rats (Table 1, 2). However, the comparative percentage increases in serum TC, TG, LDL-C, VLDL-C and K+ concentrations obtained from female rats were observed to be significantly higher (p<0.05) compared to the values obtained for male gender following exposure to gasoline vapours (Fig. 1).


Table 1: Effect of gasoline vapours on serum lipid profile and atherogenic index in male and female rats
Image for - Exposure to Gasoline Vapours: A Potential Risk Factor for Atherosclerosis in Male and Female Rats
All values are expressed as Mean±SEM, n = 7, *p<0.05 compared with controls. Mc: Male control, Mt: Male test, Fc: Female control, Ft: Female test, TC: Total cholesterol, TG: Triglycerides, LDL-C: Low density lipoprotein-cholesterol, VLDL-C: Very low density lipoprotein-cholesterol, HDL-C: High density lipoprotein-cholesterol, AIP: Atherogenic index of plasma

Table 2: Effect of gasoline vapours on some serum electrolytes profile in male and female rats
Image for - Exposure to Gasoline Vapours: A Potential Risk Factor for Atherosclerosis in Male and Female Rats
All values are expressed as Mean±SEM, n = 7, *p<0.05 compared with controls. Mc: Male control, Mt: Male test, Ec: Female control, Ft: Female test

Image for - Exposure to Gasoline Vapours: A Potential Risk Factor for Atherosclerosis in Male and Female Rats
Fig. 1: Comparative percentage increase in serum lipid profile and artherogenic index in male and female rats exposed to gasoline vapours

Also, the comparative percentage decrease in serum HDL-C, Na+ and Cl¯ concentrations obtained from female rats (55.4±2.7, 27.8±3.8 and 4.7±1.8%, respectively) were as well observed to be significantly higher (p<0.05) compared to the comparative percentage decreases obtained for the male rats (45.7±2.3, 24.6±3.5 and 2.9±1.2%, respectively) exposed to gasoline vapours.

The result of this study also showed that the TG/HDL-C ratio and Atherogenic Index of Plasma (AIP) were significantly increased (p<0.05) in both male and female rats following exposure to the vapours (Table 1). From these results, it is evidenced that exposure to gasoline vapours may cause hyperlipidaemia, hyperkalaemia, hyponatraemia and hypochloraemia in rats model. These adverse conditions are also observed to be sex-dependent, with the female being more vulnerable. The hyperlipidaemia, as seen in increased TG/HDL-C ratio and AIP, hyperkalaemia reported in this study to be associated with exposure to gasoline vapours, suggests that gasoline vapours is one of the risk factors for atherosclerosis.

DISCUSSION

Hyperlipidaemia is well known to be one of the major risk factor for atherosclerosis and cardiovascular disease. Hence, any condition of life that causes hyperlipidermia may therefore be considered to be among the causative or risk factor for atherosclerosis. The present study was designed to assess the comparative atherosclerotic risk associated with inhalation and whole body exposure to gasoline vapours in male and female rats. The results of this study showed that exposure to gasoline vapours caused increase in serum total cholesterol (hypercholesterolaemia), LDL-C, VLDL-C, triglycerides, Atherogenic Index of Plasma (AIP) and K+, as well as decrease in serum HDL-C, Na+ and Cl¯ levels in male and female rats. Increase in AIP value have been reported to be associated with different cases of cardiovascular diseases (Dobiáová and Frohlich, 2001; Dobiáová, 2004; Tan et al., 2004). This observation indicated that exposure to gasoline vapours is associated with hyperlipidaemia, hyponatraemia, hypochloraemia and hyperkalaemia; thereby describing its atherogenic potential. However, the female gender is observed to be more adversely affected than the males.

In this study, exposure to gasoline vapour is considered a crucial factor responsible for hyperlipidaemia in the atherosclerotic risk factor profile and consequently for the increase in atherosclerotic risk. It has been reported that hypercholesterolaemia and smoking are two major risk factors for the development of atherosclerosis and both have been shown to be associated with impaired endothelial function (Zeiher et al., 1995; Heitzer et al., 1996, 1999, 2001). The observations made in this study agree with our previous report that exposure to gasoline vapours alters the normal serum lipid profile and causes oxidative stress in hepatocyte of male and female rats (Uboh et al., 2007b). The results reported in this study also indicated that exposure to gasoline vapours have a similar atherosclerotic effect as that reported for smoking (Zeiher et al., 1995; Heitzer et al., 1996, 1999, 2001). Oxidative modification of LDL-C has also been shown to be an important step in promoting atherosclerosis (Witzum, 1994; Stocker and Keaney, 2004). Also increased vascular production of super-oxide anion has been implicated as contributing to impaired endothelium-dependent vascular relaxation in animal models of hypercholesterolaemia (Ohara et al., 1993). In our previous study, a high extent of lipid peroxidation, evidenced in elevated level of malonyl dialdehyde (MDA) and reduced superoxide dismutase (SOD) activity in rats exposed to gasoline vapours was reported (Uboh et al., 2007b). Hence, the atherosclerotic condition observed in this study may be attributed to oxidative modification of lipoproteins which promotes endothelial dysfunction.

Hyperkalaemia, hyponatraemia and hypochloraemia are also reported in this study to be associated with exposure to gasoline vapours in the rat model. These disorders in electrolytes balance are also known to be implicated in atherosclerotic condition. Eteng et al. (2006) demonstrated the relationship between serum electrolytes (Na+, K+ and HCO3¯) and serum lipid profile. Na+ and Cl¯ excretion from the body is reported to be a function of arterial blood pressure (Guyton, 2006).

Moreover, Na+ depletion is reported to stimulate rennin release and subsequent production of Angiotensin II, which is a potent vasoconstrictor (Guyton, 2006). Angioensin II and small increase in plasma K+ is known to stimulate the production/release of aldosterone. The Rennin-Angiotensin System (RAS) and particularly the Angiotensin II is reported to play a key role in blood pressure homeostasis and atherogenesis through its hypertensive effect (Mazzolai et al., 2004; Nussberger et al., 2008). Also, primary hyperaldosteronism is considered to be associated with residual hypertension. It is interesting to note that several of the proposed mechanism for atherogenesis are similar to those associated with Angiotensin II mediated events (Su et al., 1998; Keidar et al., 2001; Mazzolai et al., 2000). More so, animal experiments and human studies both indirectly and directly demonstrated that pharmacological blockade of the RAS has been of beneficial effect on atherosclerosis (Strawn et al., 2000; Yusuf et al., 2000). From these reports, it may be suggested that the atherosclerotic condition reported in this study is likely to be caused by the RAS stimulating effect of hyponatraemia and hyperkalaemia associated with exposure to gasoline vapour.

The result of this study also showed that the atherosclerotic risk of gasoline vapours is sex-dependent in rats. This observation supported our earlier reports that haematotoxicity and hepatotoxicity effects associated with exposure to gasoline vapours are sex-dependent, with females being more adversely affected (Uboh et al., 2007a, b). The specific mechanism of this sex-dependent effect is not very clear. However, Lambrinoudaki et al. (2006) reported that increased androgenicity is associated with unfavourable cardiovascular risk profile, while high endogenous estradiol is related to a pro-atherogenic lipid profile in healthy postmenopausal women. It has also been reported that pre-menopausal women have a lower incidence of cardiovascular disease (CVD) compared with men of the same age (Matthews et al., 1989). According to Connor and Bush (1991), Liu (2001) and Warren and Halpert (2004), female sex hormones deficiency, as in menopausal state, is associated with a pro-atherogenic lipid profile characterized principally by lower HDL-C, higher total cholesterol, triglycerides, LDl-C and VLDL-C levels. In our previous study, we reported that exposure to gasoline vapours caused significant reduction in steroidal sex hormones in female rats and increase in sex hormones in male rats models (Uboh et al., 2007c). Hence, the sex-dependent atherosclerotic risk of gasoline vapour reported in this study may be attributed to increase adverse effect of the vapours’ constituents on sex hormonal system in female rats than the males.

From the observations made in this study it may apparently be concluded that exposure to gasoline vapours is also among the risk factors for atherosclerosis and hence cardiovascular disease. This study also make it clear that the atherosclerotic risk associated with exposure to gasoline vapours is sex-dependent in rats models and that he female gender is at greater risk.

REFERENCES

  1. AOAC, 1990. Official Methods of Analysis. 15th Edn., Association of Official Analytical Chemists, Washington, DC., USA., pp: 200-210
    Direct Link  |  


  2. Connor, E.B. and T.L. Bush, 1991. Estrogen and coronary heart disease in women. JAMA, 265: 1861-1867.
    Direct Link  |  


  3. Carballo, M.A., M.L. Nigro, M.B. Dicarlo, S. Gasparini and S. Campos et al., 1995. Ethylene oxide II: Cytogenic and biochemical studies in persons occupationally exposed. Environ. Mol. Mutat., 25: 81-97.


  4. Azevedo, P.A.D., A.L. Tannhauser, S.L. Tannhauser and H.M.T. Barros, 1996. Haematological alterations in rats from xylene and benzene. Vet. Hum. Toxicol., 38: 340-344.
    PubMed  |  


  5. Dobiasova, M., 2004. Atherogenic index of plasma [Log(Triglycerides/HDL-Cholesterol)]: Theoretical and practical implications. Clin. Chem., 50: 1113-1115.
    CrossRef  |  PubMed  |  Direct Link  |  


  6. Dobiasova, M. and J. Frohlich, 2001. The plasma parameter log (TG/HDL-C) as an atherogenic index: Correlation with lipoprotein particle size and esterification rate inapob-lipoprotein-depleted plasma (FERHDL). Clin. Biochem., 34: 583-588.
    CrossRef  |  PubMed  |  Direct Link  |  


  7. Eteng, M.U., H.A. Ibekwe, T.E. Amatey, B.J. Bassey, F.U. Uboh and D.U. Owu, 2006. Effect of vitamin C on Serum lipids and electrolyte profile of Albino Wistar Rats. Niger. J. Physiol. Sci., 21: 15-19.
    PubMed  |  Direct Link  |  


  8. Friedewald, W.T., R.I. Levy and D.S. Fredrickson, 1972. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 18: 499-502.
    CrossRef  |  PubMed  |  Direct Link  |  


  9. Frohlich, J. and M. Dobiasova, 2003. Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography. Clin. Chem., 49: 1873-1880.
    CrossRef  |  


  10. Gambhir, D.S., J.K. Gambhir and R. Sudha, 2001. Dyslipidaemia and coronary heart disease management of issues from Indian prospective. Indian Heart J., 52: 515-516.


  11. Gaziano, J.M., C.H. Hennekens, C.J.O. Donnell, J.L. Breslow and J.E. Buring, 1997. Fasting triglycerides high-density lipoprotein and risk of myocardial infarction. Circulation, 96: 2520-2525.
    Direct Link  |  


  12. Gilling, L., P. Suwattee, C. de Souza, S. Asnani and V. Fonseca, 2002. Effects of the thiazolidinediones on vascular risk factors. Am. J. Cardiovasc Drugs, 2: 149-156.
    PubMed  |  


  13. Guyton, A.C., 2006. Textbook of Medical Physiology. 11th Edn., Elsevier, India, Philadelphia


  14. Heitzer, T., S.Y. Herttuala, J. Luoma, S. Kurz and T. Munzel et al., 1996. Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia role of oxidized LDL. Circulation, 93: 1346-1353.
    PubMed  |  


  15. Heitzer, T., S.Y. Herttuala, E. Wild, J. Luoma and H. Drexler, 1999. Effect of vitamin E on endothelial vasodilator function in. [patients with hypercholesterolemia, chronic smoking or both. J. Am. Coll. Cardiol., 33: 499-505.
    PubMed  |  Direct Link  |  


  16. Heitzer, T., T. Schlinzig, K. Krohn, T. Meinertz and T. Munzel, 2001. Endothelial dysfunction oxidative stress and risk of cardiovascular events in patients with coronary artery disease. Circulation, 104: 2673-2678.
    Direct Link  |  


  17. Keidar, S., R. Heinrich, M. Kaplan, T. Hayek and M. Aviram, 2001. Angiotensin II administration to atherosclerotic mice increases macrophage uptake of oxidized ldl a possible role for interleukin-6. Arterioscler Thromb. Vasc. Biol., 21: 1464-1469.
    Direct Link  |  


  18. Lambrinoudaki, I., G. Christodoulakos, D. Rizos E. Economou and J. Argeitis et al., 2006. Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women. European J. Endocrinol., 154: 907-916.
    Direct Link  |  


  19. Liu, Y., J. Ding, T.L. Bush, T.L. Bush, J.C. Longenecker, F.J. Nieto, S.H. Golden and M. Szklo, 2001. Relative androgen excess and increased cardiovascular risk after menopause a hypothesized relation. Am. J. Epidemiol., 154: 489-494.
    Direct Link  |  


  20. Matthews, K.A., E. Meilahn, L.H. Kuller, S.F. Kelsey, A.W. Caggiula and R.R. Wing, 1989. Menopause and risk factors for coronary heart disease. New. Engl. J. Med., 321: 641-646.
    Direct Link  |  


  21. Mazzolai, L., M.A. Duchosal, M. Korber and K. Bouzourene, J.F. Aubert et al., 2004. Endogenous angiotensin II induces atherosclerotic plaque vulnerability and elicits a Th1 response in ApoE-/- Mice. Hypertension, 44: 277-282.
    Direct Link  |  


  22. Mazzolai, L., T. Pedrazzini, F. Nicoud, G. Gabbiani, H.R. Brunner and J. Nussberger, 2000. Increased cardiac angiotensin II levels induce right and left ventricular hypertrophy in normotensive mice. Hypertension, 35: 985-991.
    Direct Link  |  


  23. Nussberger, J., J.F. Aubert, K. Bouzourene, M. Pellegrin, D. Hayoz and L. Mazzolai, 2008. Renin inhibition by aliskiren prevents atherosclerosis progression comparison with irbesartan atenolol and amlodipine. Hypertension, 51: 1306-1311.
    Direct Link  |  


  24. Ohara, Y., T.E. Peterson and D.G. Harrison, 1993. Hypercholesterolemia increases endothelial superoxide anion production. J. Clin. Invest., 91: 2546-2551.


  25. Rabble, G.K. and O. Wong, 1996. Leukaemia mortality by cell type in petroleum workers with potential exposure to benzene. Environ. Health Perspect., 104: 1381-1392.
    Direct Link  |  


  26. Rader, D.J., 2002. High-density lipoprotein and atherosclerosis. Am. J. Cardiol., 92: 62-72.
    PubMed  |  


  27. Richmond, W., 1973. Cholesterol enzymatic colorimetric test chop-PAP method of estimation of total cholesterol in serum. Clin. Chem., 191: 1350-1356.


  28. Rothman, N., G.L. Li, M. Dosemeci, W.E. Bechtold and G.E. Marti et al., 1996. Hematotoxicity among Chinese workers heavily exposed to benzene. Am. J. Ind. Med., 29: 236-246.
    PubMed  |  Direct Link  |  


  29. Stocker, R. and J.F. Keaney Jr., 2004. Role of oxidative modifications in atherosclerosis. Physiol. Rev., 84: 1381-1478.
    PubMed  |  Direct Link  |  


  30. Strawn, W.B., M.C. Chappell, R.H. Dean, S. Kivlighn and C.M. Ferrario, 2000. Inhibition of early atherogenesis by losartan in monkeys with diet-induced hypercholesterolemia. Circulation, 101: 1586-1593.
    Direct Link  |  


  31. Su, E.J., D.M. Lombardi, J. Siegal and S.M. Schwartz, 1998. Angiotensin II induces vascular smooth muscle cell replication independent of blood pressure. Hypertension, 31: 1331-1337.
    Direct Link  |  


  32. Synder, R. and C.C. Hedli, 1996. An overview of benzene metabolism (Review). Environ. Health Perspect., 104: 1165-1171.
    Direct Link  |  


  33. Tan, M.H., D. Johns and N.B. Glazer, 2004. Pioglitazone reduces atherogenic index of plasma in patients with type 2 diabetes. Clin. Chem., 50: 1184-1188.
    Direct Link  |  


  34. Nasiruddin, M.T. and N. Ahmad, 2006. Effect of an unani formulation on lipid profile in rat. Indian J. Pharmacol., 38: 56-57.
    Direct Link  |  


  35. Uboh, F.E., M.I. Akpanabiatu and Y. Alozie, 2008. Comparative effect of gasoline vapours on renal functions in male and female albino wistar rats. J. Pharmacol. Toxicol., 3: 478-484.
    CrossRef  |  Direct Link  |  


  36. Uboh, F.E., M.I Akpanabiatu, I.J. Atangwho, P.E. Ebong and I.B. Umoh, 2007. Effect of gasoline vapours on serum lipid profile and oxidative stress in hepatocytes of male and female rats. Acta Toxicol., 15: 13-18.


  37. Uboh, F.E., M.I. Akpanabiatu, P.E. Ebong and I.B. Umoh, 2007. Gender differences in the haematotoxicity and weight changes associated with exposure to gasoline vapours in wistar albino rats. Acta Toxicol., 15: 125-131.
    Direct Link  |  


  38. Uboh, F.E., M.I. Akpanabiatu, I.S. Ekaidem, P.E. Ebong and I.B. Umoh, 2007. Effect of inhalation exposure to gasoline on sex hormones profile in wistar albino rats. Acta Endocrinol., 3: 23-30.
    Direct Link  |  


  39. Vogel, A.I., 1960. A Textbook of Quantitative Inorganic Analysis. 3rd Edn., Longman Group Ltd., London, pp: 882-885


  40. Warren, P.M. and S. Halpert, 2004. Hormone replacement therapy controversies pros and cons. Best Practice Re. Clin. Endocrinol. Metabolism, 18: 317-332.
    PubMed  |  


  41. Witzum, J.L., 1994. The oxidation hypothesis of atherosclerosis. Lancet, 344: 793-795.
    CrossRef  |  PubMed  |  Direct Link  |  


  42. Yusuf, S., P. Sleight, J. Pogue, J. Bosch, R. Davies and G. Dagenais, 2000. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N. Engl. J. Med., 342: 145-153.
    CrossRef  |  Direct Link  |  


  43. Zahlsen, K., A.M. Nilsen, I. Eide and O.G. Nilsen, 1993. Inhalation kinetics of carbon 8 to carbon 10, L-alkanes and iso-alkanes in the rats after repeated exposures. Pharamacol. Toxicol., 73: 163-168.


  44. Zeiher, A.M., V. Schachinger and J. Minners, 1995. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation, 92: 1094-1100.
    PubMed  |  


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