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.

IntroductionAluminum (Al) is a ubiquitous metal on earth. Al and its salts are commonly used in various daily applications, such as water treatment, wood preservation, food additives, toothpastes, antiperspirants, shampoos, vitamins, medications, vaccines, antacids, phosphate binders, buffered aspirin products, packaging materials, or as fillers in plastics

Aluminum (Al), an ubiquitous element in nature, enters the body primarily through gastrointestinal tract, respiratory system and skin. Being a powerful neurotoxin for human brain, Al was reported to be involved in the etiology of Alzheimer's disease due to its easy access and accumulation in the central nervous system. Melatonin (Mel) is a tryptophan-derived neurohormone in animals and plants, and produced in the pineal gland of all mammalian species. The present study examines the effects of Mel on Al-induced oxidative stress, inflammation, tissue factor production and brain damage in rat brain. Wistar albino rats were divided into four groups. Group I: control animals; Group II: rats injected with 10 mg/kg Mel; Group III: rats injected with 5 mg/kg Al2(SO4)3; and Group IV: rats injected combination of Al and Mel (5 mg/kg Al2(SO4)3 and 10 mg/kg Mel). Animals were injected three times a week for one month. At the end of the month, rats were sacrificed, their brains were removed. It was found that lipid peroxidation, protein carbonyl, advanced oxidation protein products, hydroxyproline levels, tissue factor, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, acetylcholine esterase, alkaline phosphatase, acid phosphatase and glucose-6-phosphate dehydrogenase activities were increased, while paraoxonase, arylesterase, sodium potassium ATPase activities and glutathione levels were decreased in the Al-treated group. Mel treatment reversed these changes by demonstrating significant antioxidant effects. Results indicated that Mel has potential therapeutic value against Al-induced oxidative stress in the rat brain tissue and these effects may be related to its antioxidant activities.