cytochrome-c-t and aluminum-phosphide

Poisoning with aluminum phosphide (AlP) has been attributed to the high rate of mortality among many Asian countries. It affects several organs, mainly heart and kidney. Numerous literature demonstrated the valuable effect of minocycline in mitigating pathological symptoms of heart and kidney disease. The aim of the present study was to evaluate the probable protective effect of minocycline on cardiac hemodynamic parameters abnormalities and renal toxicity induced by AlP-poisoning in the rat model. AlP was administered by gavage at 12 mg/kg body weight followed by injection of minocycline for two interval times of 12 and 24 h, at 40, 80, 120 mg/kg body weight. Electrocardiographic (ECG) parameters were monitored, 30 min after AlP gavage for 6 h using an electronic cardiovascular monitoring device. Kidney tissue and serum were collected for the study of histology, mitochondrial complexes I, II, IV, lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity, ADP/ATP ratio, mitochondrial cytochrome c release, apoptosis, lactate, BUN, and Cr levels. The results demonstrated that AlP induces ECG abnormalities, and failure of heart rate and blood pressure, which improved significantly by minocycline. Minocycline treatment significantly improved complexes I, IV, MPO and LDH activities, and also reduced the ADP/ATP ratio, lactate level, release of cytochrome c, and apoptosis in the kidney following AlP-poisoning. Also, the histological results showed an improvement of kidney injury in minocycline treated groups. In conclusion, the findings of this study showed that minocycline could improve cardiac hemodynamic abnormalities and kidney injury following AlP-poisoning, suggesting minocycline might be a possible candidate for the treatment of AlP-poisoning.

Topics: Acute Kidney Injury; Aluminum Compounds; Animals; Apoptosis; Blood Pressure; Cytochromes c; Electrocardiography; Heart; Heart Rate; Kidney; L-Lactate Dehydrogenase; Lactic Acid; Male; Minocycline; Phosphines; Protective Agents; Rats, Wistar

Aluminum phosphide (AlP), a widely used fumigant and rodenticide leads to high mortality if ingested. Its toxicity is due to phosphine liberated when it comes in contact with moisture. The exact mechanism of action of phosphine is not known. In this study male Wistar rats were used. The animals received a single dose (20mg AlP/kg body weight i.g.) orally. Basic serum biochemical parameters, activity of mitochondrial complexes, antioxidant enzymes and parameters of oxidative stress, individual mitochondrial cytochrome levels were measured along with tissue histopathology and immunostaining for cytochrome c and compared with controls. The serum levels of creatinine kinase-MB, lactate dehydrogenase, magnesium and cortisol were higher (p<0.01); the activities of mitochondrial complexes I, II, IV were observed to be significantly decreased in liver tissue in treated rats (p<0.01). The activity of catalase was lower (p<0.05) with a significant increase in lipid peroxidation (p<0.05) whereas superoxide dismutase and glutathione peroxidase were unaffected in them. There was a significant decrease in all the cytochromes in brain and liver tissues (p<0.05) with the exception of cytochrome b in brain, the levels of which remained same. Histopathology revealed congestion in most organs with centrizonal hemorrhagic necrosis in liver. Ultra structural changes indicating mitochondrial injury was observed in heart, liver and kidney tissues. There was also a marked reduction in the cytochrome-c immunostaining compared to the controls. Toxicity due to AlP appears to result as a consequence of both-energy insufficiency and oxidative stress, with a possible and preferential interaction with the tissue cytochromes.

Topics: Aluminum Compounds; Animals; Brain; Catalase; Cytochromes c; Electron Transport Complex IV; Glutathione Peroxidase; L-Lactate Dehydrogenase; Lipid Peroxidation; Liver; Male; Microscopy, Electron; Mitochondria, Liver; NADH Dehydrogenase; Oxidative Phosphorylation; Pesticides; Phosphines; Rats; Rats, Wistar; Succinate Dehydrogenase; Superoxide Dismutase