Search

Aluminum has toxic potential on humans and animals when it accumulates in various tissues. It was shown in a number of studies that aluminum causes oxidative stress by free radical formation and lipid peroxidation in tissues and thus may cause damage in target organs. Although there are numerous studies investigating aluminum toxicity, biochemical mechanisms of the damage caused by aluminum have yet to be explained. Melatonin produced by pineal gland was shown to be an effective antioxidant. Since kidneys are target organs for aluminum accumulation and toxicity, we have studied the role of melatonin against aluminum-induced renal toxicity in rats. Wistar albino rats were divided into five groups. Group I served as control, and received only physiological saline; group II served as positive control for melatonin, and received ethanol and physiological saline; group III received melatonin (10 mg/kg); group IV received aluminum sulfate (5 mg/kg) and group V received aluminum sulfate and melatonin (in the same dose), injected three times a week for 1 month. Administration of aluminum caused degenerative changes in renal tissues, such as increase in metallothionein immunoreactivity and decrease in cell proliferation. Moreover, uric acid and lipid peroxidation levels and xanthine oxidase activity increased, while glutathione, catalase, superoxide dismutase, paraoxonase 1, glucose-6-phosphate dehydrogenase, and sodium potassium ATPase activities decreased. Administration of melatonin mostly prevented these symptoms. Results showed that melatonin is a potential beneficial agent for reducing damage in aluminum-induced renal toxicity.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine, which has the ability to produce cytotoxicity via induction of cell death and cell cycle arrest. Blocking the synthesis of protective proteins through a transcriptional inhibitor such as actinomycin D (Act D) sensitizes many cell types to TNF-α toxicity. Teduglutide, h[Gly(2)]GLP-2, is a protease-resistant synthetic analog of glucagon-like peptide-2 (GLP-2) which is an intestinotrophic peptide. In this study, we evaluated this potential of GLP-2 on apoptosis, cell proliferation, and oxidant-antioxidant system on a mouse model of intestinal injury induced by TNF-α/Act D. The intestinal injury was induced by intraperitoneal administration of 15 μg/kg TNF-α and 800 μg/kg Act D per mouse. Animals were injected subcutaneously 200 μg/kg h[Gly(2)]GLP-2 every 12 h for 10 consecutive days prior to the administration of TNF-α and Act D. The model of intestinal injury induced by TNF-α/Act D, which is the new animal model for the intestinal disorders, was characterized by the degeneration of intestinal mucosa, an increase in apoptotic index, expression of active caspase-3, lipid peroxidation and glutathione (GSH) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities; a decrease in cell proliferation and catalase (CAT) activity. h[Gly(2)]GLP-2 pretreatment prevented the TNF-α/Act D-induced oxidative injury by a significant reduction in the intestinal injury, apoptotic index, expression of active caspase-3, lipid peroxidation and GSH levels, GPx and SOD activities; a markedly increase in cell proliferation, and CAT activity. These results demonstrate that GLP-2 has a protective, antiapoptotic, proliferative, and antioxidant effects against to TNF-α/Act D-induced intestinal injury. It is suggested that GLP-2 may potentially be useful as a therapeutic agent in TNF-α-mediated intestinal disorders.