N-acetylcysteine pretreatment ameliorates mercuric chloride-induced oxidative renal damage in rats.

Abstract

The effectiveness of the antioxidant thiol, N-acetylcysteine (NAC), in enhancing methylmercury (CH3HgCl) excretion and its utility as a possible antidote in CH3HgCl poisoning has been reported. NAC, however, has been reported to be ineffective in accelerating excretion of divalent toxic metals, including inorganic mercury, Hg2+. In this study, we evaluated the possible protective effect of short-term pretreatment with NAC against mercuric chloride (HgCl2) toxicity in rat model. This is aimed at determining its chemopreventive or prophylactic benefit in situations of high risk exposure (occupational/industrial) to mercury. Rats were divided into three treatment groups. Group I received saline (10 ml/kg) and served as control. Group II received HgCl2 (5mg/kg) and group III received NAC (10mg/kg) plus (5mg/kg). All administration was via intraperitoneal (i.p.) injection. Saline and NAC were administered for 5days and HgCl2 was administered to rats in groups II and III on the 5th day. Animals were sacrificed 24 hours after HgCl2 injection and samples obtained for biochemical evaluation. Results revealed that single i.p. injection of HgCl2 induced significant renal oxidative damage resulting in significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), depletion of reduced glutathione (GSH) and increase in malondialdehyde (MDA) levels in these rats. The activities of glucose-6-phosphatase (G6Pase) and 5'-nucleotidase (5'-NTD) (markers of microsomal damage) also decreased in these HgCl2 treated rats. The oxidative damage induced by HgCl2 led to significant alterations in renal histology and caused functional impairment (indicated by elevated blood urea nitrogen (BUN) and serum creatinine) in these rats. NAC was effective in attenuating the oxidative damage, functional impairments and histopathological changes that characterized HgCl2 intoxication in this study. Renal antioxidant defense system was re-enforced by NAC, leading to increase in the activities of SOD, CAT, GST and decreases in GSH depletion and MDA level. Our results therefore reveal the ameliorative effect of NAC pretreatment against HgCl2 toxicity in vivo, thus, suggesting its usefulness as a possible chemoprophylactic agent during occupational or industrial exposure to inorganic mercury.

• Authors: M Ekor, O A Adesanoye, E O Farombi
• Journal: African journal of medicine and medical sciences (Afr J Med Med Sci) Vol. 39 Suppl Pg. 153-60 (Dec 2010) ISSN: 0309-3913 [Print] Nigeria
• PMID: 22416658 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Antioxidants
• Malondialdehyde
• Mercuric Chloride
• Catalase
• Superoxide Dismutase
• Glucose-6-Phosphatase
• Mercury
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology, therapeutic use)
• Animals
• Antioxidants (metabolism, pharmacology)
• Catalase (metabolism)
• Chemoprevention
• Disease Models, Animal
• Glucose-6-Phosphatase (metabolism)
• Glutathione (metabolism)
• Injections, Intraperitoneal
• Kidney (drug effects, injuries, pathology)
• Lipid Peroxidation (drug effects)
• Male
• Malondialdehyde (metabolism)
• Mercuric Chloride (toxicity)
• Mercury
• Mercury Poisoning (prevention & control)
• Oxidation-Reduction
• Random Allocation
• Rats
• Rats, Wistar
• Superoxide Dismutase (metabolism)