Sexual dimorphism in inorganic mercury toxicokinetics and the attendant lipotoxic and non-lipotoxic dyslipidemia in the rat.

The influence of variability in the biology of living organisms is poorly appreciated in toxicology. However, multiple lines of evidence indicate that sex-differences modulate toxicokinetics and toxicodynamics from cellular/molecular to whole animal levels resulting in different toxic responses of living organisms to xenobiotics exposure. In order to investigate the influence of sex in inorganic mercury (Hg) exposure, male and female Wistar rats were exposed to 0.5, 1.0 and 1.5 mg Hg/kg body weight orally as HgCl2 twice a week for 12 weeks. Higher Hg levels in the females (except heart) as compared to males were observed in the animals. At the highest dose of inorganic Hg, female renal Hg content was 3.3 times higher than that of the males. Mixed sexual dimorphism characterised circulating-lipid- and organ-lipid lipotoxic and non-lipotoxic dyslipidemia. The highest dose of inorganic Hg, induced hypercholesterolemia in the males as opposed to hypocholesterolemia in the female. Plasma and erythrocyte free fatty acids increased in both sexes, although the increase was more pronounced in the male. Reverse cholesterol transport was inhibited in the male at the highest dose of Hg, whereas female HDL became enriched with cholesterol. Female erythrocytes had all their lipids increased, whereas only male erythrocyte triglyceride increased. Brain cholesterol and phospholipids, and splenic phospholipids were depleted in both sexes. Our findings indicate that inorganic Hg exposure appears to affect Hg and lipid kinetics differently in both sexes, thus underscoring the need to develop sex-tailored approaches in the treatment of metal toxicosis and its metabolic outcomes.

Ionoregulatory Disruption and Acetylcholinesterase Activity in Aluminium Toxicity: Effects of Vitamins C and E.

To investigate the effects of vitamin C and E on electrolyte profile and the activity of acetylcholinesterase (AChE) in Aluminium (Al) chloride exposed rats, thirty-six male rats were used for this study. The animals were randomly grouped into six (n=6); group I (Control) was given normal saline. Group II (Al only) was exposed to 20mg/kg body weight (BW) of Al. Groups III (Vitamin C only) and IV (Vitamin E only) were administered 200mg/kg BW of vitamin C and vitamin E respectively. Groups V (Al + Vit C) and VI (Al + Vit E) were exposed to 20mg/kg Al and were treated with 200mg/kg vitamin C and vitamin E respectively. Al exposure resulted in a significant (P<0.05) increase in plasma calcium and erythrocyte magnesium concentrations compared with control. The erythrocyte sodium concentration of group treated with Al alone was significantly (P<0.05) higher by 2.01folds than the control group. While the two vitamins were unable to correct the disruption in calcium homeostasis, they ameliorated the intracellular levels of sodium and magnesium ions. A reduction in the activity of AChE (1378.90±130.02U/L)was observed in erythrocyte of the group exposed to Al when compared to the control (1968.80±283.72U/L). Treatment with vitamins C and E further inhibited erythrocyte AChE activity by 34% and 39% respectively compared to a 30% inhibition by Al only. Positive associations were observed between erythrocyte magnesium and blood sodium, and plasma calcium and erythrocyte sodium levels. Negative associations were however observed between plasma AChE activity and erythrocyte sodium and magnesium levels. In conclusion, vitamins C and E ameliorated ionoregulatory disruptions caused by sub-acute aluminium on only erythrocyte sodium and magnesium levels but not on plasma calcium level and erythrocyte acetylcholinesterase activity.

Lipid peroxidation in brain tissue following administration of low and high doses of arsenite and L-ascorbate in wistar strain rats.

This study aimed at investigating the mechanism by which sodium arsenite induces brain injury and the role of L-ascorbate. Thirty adult (n=5) Wistar rats weighing between 140 and 160 g were used. Group 1 neither received sodium arsenite nor L-ascorbate (control), group 2 was administered low dose of arsenite only, group 3 received high dose of arsenite only, group 4 was administered L-ascorbate only, group 5 was administered low dose of arsenite and L-ascorbate, and group 6 received high dose of arsenite and L-ascorbate. M0 alon dialdehyde, MDA, levels were significantly increased in rats treated with high dose of arsenite when compared with those treated with low dose of arsenite. However, all treated groups except those treated with L-ascorbate only showed significant increase in MDA levels when compared with the control group. Rats treated with high dose of arsenite and L-ascorbate showed a significantly higher MDA level than those treated with low dose of arsenite and L-ascorbate. However, catalase activity, body weight gain, brain weight and mean food consumption were comparable across all groups. Brain tissue total protein was similar in all groups except in both groups treated with high dose of arsenite, where they were significantly reduced when compared with the control group. I0 n conclusion, sodium arsenite treatment induces brain injury via a mechanism associated with lipid peroxidation, but not catalase-dependent. However, L-ascorbate ameliorates arsenite-induced oxidative injury in the brain. L-ascorbate antioxidative potential in alleviating arsenite-induced brain injury is dependent on the concentration of arsenite.