Role of melatonin against oxidative tissue damage induced by Cleistanthus collinus in rat brain.
OBJECTIVE
The leaves of Cleistanthus collinus, an extremely poisonous plant are consumed for suicidal purposes in various parts of India. The mortality rate is high and there is no antidote. In this study, we attempted to delineate oxidative stress as a possible mechanism of action of C. collinus toxicity in rats and the role of melatonin against injury to brain and heart caused by C. collinus.


METHODS
Adult Wistar rats (130 -200 g, n = 6 per group) of either sex were used. C. collinus at 8 mg/kg body weight (LD(50)) was administered orally followed by melatonin 15 mg/kg body weight ip or cysteine 500 mg/kg body weight ip (standard) after 2 h. Malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase and catalase levels in brain, heart and blood were estimated and histopathological examinations (brain and heart) were done. For the survival study, rats were treated with increasing doses of melatonin (5, 10 and 15 mg/kg body weight ip) following a lethal dose of C. collinus (10.5 g/kg body weight orally).


RESULTS
The results showed a significant (P<0.05) increase in blood and brain MDA levels and decrease in tissue GSH in the LD(50) group. This was accompanied by marked gliosis, spongiform necrosis and lymphocytic inflammatory infiltrates in brain and marked congestion, inflammation and muscle necrosis in heart. Melatonin significantly (P<0.05) reduced lipid peroxidation and reversed the histopathological changes induced by C. collinus in the brain but not in the heart.


CONCLUSIONS
Our results suggest that oxidative mechanisms play an important role in C. collinus induced tissue damage and melatonin, by balancing oxidant-antioxidant status ameliorates oxidative organ injury in brain due to C. collinus toxicity.
Jayanthi
M
M
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India. drjayanthi2008@gmail.com
Raveendran
R
R
Basu
Debdatta
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity*; D018515:Plant Leaves / Q000737:chemistry; D010947:Plants, Toxic / Q000033:anatomy & histology / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D018696:Neuroprotective Agents; D010936:Plant Extracts; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D008550:Melatonin; D003545:Cysteine