Effect of lead acetate on the histological structure of the adrenal cortex of male albino rats and the possible protective role of vitamin E

Lead is a nonessential, toxic, heavy metal widely distributed in the environment and chronic exposure to low levels of this agent is of public concern in many countries. Lead is a toxic agent with multiple target organs such as the gastrointestinal tract, the hematopoietic system, the immune system, the kidneys and the endocrine, reproductive and nervous systems. This study aimed to study the toxic effect of lead acetate on the histological structure of the adrenal cortex of adult male albino rats and the possible protective role of vitamin E in the these changes. Fifty male albino rats were divided into three groups: group I [10 animals] was used as a control, group II [20 animals] received lead acetate alone, and group III [20 animals] received the same lead acetate dose and supplementation with vitamin E, 6 h before lead acetate was given. At the end of the experiment [3 months], rats were killed and the adrenal glands were obtainerl. In the group that received lead acetate, the histological structure of the three zones of the adrenal cortex was markedly affected when examined by both light and electron microscopes. In the zona glomerulosa, there was loss of architecture and marked destruction of most of the cells. The electromicrograph of both the zona glomerulosa and fascicula showed degenerated mitochondria and vacuolation of the cytoplasm. These changes were not completely reversed with the use of vitamin E. The use of vitamin E may have little beneficial effect on the protection of the suprarenal cortex against lead acetate toxicity

Age related changes and melatonin

Melatonin [N-acetyl-5-methoxy-tryptamine] is a neurohormone that is secreted by a small gland in the center of the brain called the pineal gland. Aging is accompanied by changes in the morphology and physiology of organs and tissues. This process might be due to the accumulation of oxidative damage induced by reactive oxygen [ROS] and reactive nitrogen species [RNS]. To assess age - related changes that occur in the lung, liver and kidney of the rat and to investigate the protective role of exogenous melatonin against these changes. Thirty five male albino rats were classified into 3 groups. Group 1 [non aged] acted as the control group, injected with normal saline intraperitoneal 3 times / week and sacrificed when aged 3 months. Group II remained untreated and sacrificed when aged 18 months. Group III was treated with melatonin [1 mg/kg] intraperitoneal 3 times / week and sacrificed when aged 18 months. The antioxidant effect of melatonin was also detected by measuring the level of nitric oxide in all groups. Group II showed marked age-related changes in the examined organs. The lung showed thickening in the wall of the alveoli with increased phagocytic and lymphocytic infiltration. The liver showed vaculation of the cytoplasm and increased phagocytic infiltration .The kidney showed atrophic glomeruli. Most of these changes were reduced in group III [treated with melatonin] except increasing the number of phagocyte especially in the lung. Melatonin also decreased the level of nitric oxide. Melatonin seems to have beneficial effects against age- related changes in the lung, liver and kidney

Role of oxidative stress in cisplatin - induced nephrotoxicity in rats

Cisplatin [cis diammine dichloroplatinum] is a potent antitumor drug. Expansion of the clinical utility of cisplatin has been limited by its toxicity where acute and chronic forms of renal injury have been described due to apoptosis. The mechanism by which it activates the myriad of apoptotic pathways remains unclear. Several studies have now documented the importance of reactive oxygen metabolites [ROM] in cisplatin-induced renal cell apoptosis. To further clarify this point the present study was conducted to evaluate the oxidative stress induced by cisplatin. Rats were treated either by high single intraperiotoneal dose [7mg/kg] or by repeated small doses [4mg/kg] twice weekly for one month. Rats were sacrificed by decapitation after 48 hours of high dose intake or 24 hours after intake repeated small doses. Kidney tissues were removed for histopathological examination, after homogenization these tissues were removed for determination of glutathione [GSH]. Blood samples were taken from rats for determination of serum level of creatinine, blood urea nitrogen [BUN] and nitric oxide [NO]. Histopathological examination of kidney tissue revealed degenerative changes with tubular change, especially in the proximal convoluted tubules. Significant elevation in serum creatinine [2.24 +/- 0.18 vs 2.12 +/- 0.18] and BUN [146 +/- 10.6 vs132 +/- 11.2] levels were observed. Administration of cisplatin in large dose or small repeated doses causes significant elevation in serum [NO] level [10.4 +/- 0.8 micro mol/l and 9 +/- 0.53 micro mol/l respectively] as well as depletion in renal [GSH] tissue levels [1.02 +/- 0.09 micro mol/l w.wt wet, weight] and 1.12 +/- 0.08 micro mol/g w.wt, respectively]. From these results, it can be concluded that single high dose or small repeated doses of cisplatin-induced nephrotoxicity was associated with induction of oxidative stress. Use of antioxidants in conjunction with cisplatin could be a value in minimizing its toxicity