Organelle specific enzyme markers as indicators of methylmercury neurotoxicity and antidotal efficacy in mice.
The efficacy of two monothiols, N-acetyl-DL-homocysteine thiolactone (NAHT) and glutathione (GSH) either alone or in combination with two vitamins, vitamin B complex and vitamin E were studied in 7 days methylmercury chloride (MMC; I mg kg) intoxicated male Swiss albino mice. Thirteen groups of animals, each containing 6 animals were used for the study. Three groups of animals were kept as control (treated either with vehicle, normal saline or olive oil). Rest of the ten groups were kept as treatment groups. All the animals were treated subcutaneously for 7 days with MMC and one group was sacrificed on the 8th day. The second group was kept without toxicant for another 7 days and were sacrificed on the 15th day. Two MMC pretoxicated groups were treated either with vitamin B complex (20 mg kg) or vitamin E (60 mg kg) and two other groups were treated with N-acetyl-DL-homocysteine thiolactone (40 mg kg) or glutathione (50 mg kg) for another 7 days. The rest of the four groups were treated with either N-acetyl-DL-homocysteine thiolactone or glutathione in combination with either vitamin B complex or vitamin E. All the animals were sacrificed on the 15th day, brain and spinal cord were dissected and estimated for acid phosphatase, alkaline phosphatase, succinic dehydrogenase and alpha mannosidases. Some of the antidotes showed significant recovery of the enzymes in one tissue while some showed significant recovery in the other tissue depicting the need for treating methylmercury poisoned animals with multi-chelation therapy rather than as a monotherapy.
Bapu
Cherian
C
Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development Centre, Thaltej Gandhinagar Highway, Thaltej Ahmedabad. 380 054, Gujarat, India.
Sood
Prem Prakash
PP
Nivsarkarl
Manish
M
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004359:Drug Therapy, Combination; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000201:enzymology* / Q000473:pathology; D015388:Organelles / Q000187:drug effects* / Q000201:enzymology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014803:Vitamin B Complex / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000931:Antidotes; D015415:Biomarkers; D008767:Methylmercury Compounds; D013438:Sulfhydryl Compounds; D014803:Vitamin B Complex; D014810:Vitamin E; C004925:methylmercuric chloride