Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus (DM). The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient, and associated with oxidative stress induced by long-term hyperglycemia. The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs, e.g. metformin, which act through this pathway. This project was designed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin. A placebo-controlled, double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups. These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone: 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo, given at bedtime for 90 days. Fasting lipid profiles and microalbuminuria (MAU) were measured before initiating the treatments (zero time) and after 30 and 90 days of treatment. Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. In conclusion, the combination of melatonin and zinc acetate, when used alone or in combination with metformin, improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients.

Objective: This study evaluated the effect of melatonin on the response of patients suffering from metabolic syndrome (MEBS) treated with metformin. Design: This study used two-armed groups in a double-blind, randomized controlled clinical trial. Materials and Methods: A randomized double-blind placebo-controlled study was carried out on female patients diagnosed as having MEBS, according to the International Diabetes Federation (IDF) diagnosing criteria of MEBS (2005), from the outpatient clinic in Al-Zahraa Teaching Hospital/Kut, Iraq. They were diagnosed utilizing laboratory and clinical investigations, then randomized into two groups. The first group (group A) was treated with metformin (500 mg) twice daily, in addition to a placebo formula once daily at bedtime for three months. The second group (group B) was treated with metformin (500 mg) twice daily after meals, in addition to melatonin (10 mg) once daily at bedtime for three months. Results: The treatment of patients with MEBS using metformin–melatonin showed an improvement in most MEBS components such as fasting serum glucose (FSG), lipid profile, and body mass index (BMI), in addition to a reduction in insulin resistance and hyperinsulinemia. Simultaneously, there were increments in serum uric acid (UA), leptin, prolactin (PRL), and estradiol levels, while serum progesterone level decreased. Furthermore, patients treated with metformin–placebo showed less improvement in the studied parameters compared to that produced due to the inclusion of melatonin in the treatment protocol. Conclusion: Melatonin improves the effect of metformin on several components of MEBS such as FSG, lipid profile, and BMI, in addition to insulin resistance and hyperinsulinemia, compared to metformin alone.

The protective effect of ginger extract against cisplatin-induced hepatotoxicity and cardiotoxicity was evaluated in 30 albino white rats(weighing 200-300 gm ) classified into 5groups (6 rats per each group). The rats were treated with 0.5g/kg/day or         1g/kg/day ginger extract orally 5 successive days before and 5 successive days after induction of toxicity with intraperitoneal (IP) injection of (10mg/kg ) cisplatin, resulted in a significant reduction in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) , total serum  billirubin(TSB) , lactate dehydrogenase (LDH) and creatine kinase(CK) enzymes in comparison with the cisplatin treated animals; ginger extract also improves the histological changes produced by cisplatin in the liver cells and cardiac muscle fiber cells  in comparison with the control .  It is  concluded that , ginger extract when used concomitantly with cisplatin protects the liver and heart against the toxicity induced by this cytotoxic drug.                                         Key wards :Ginger, Cisplatin,Oxidative Stress.

Drug –induced nephrotoxicity is an important cause of renal failure. Aminoglycoside antibiotics, such as amikacin, which causes ototoxicity and nephrtotoxicity as a main side effects, this is focused on the use of natural materials as antioxidants against the toxic oxidative action that exert a cell damaging effect. The most important one of these materials is the honey. The aim of this work is to evaluate the antioxidant effects of honey against amikacin – induced nephrotoxicity.18 albino rats divided into 3 groups (6 rats per each group), group 1 received I.P daily dose of normal saline (control), group 2 received (35  mg/kg/day) I.P dose of amikacin ,and group 3 received (35mg/kg/day) of amikacin I.P dose in combination with oral dose of honey(500mg/kg/day) for 2 weeks. All animals (at 15th day) were anesthetized by ether and sacrificed; blood samples were collected for the subsequent measurement of the serum creatinine, urea, malneldehyde (MDA) and glutathione (GSH) while an isolated kidney was kept in 10 % of formaldehyde for the histopathological examination. This study showed that amikacin causes nephrotoxicity represented by elevation of serum level of creatinine and urea, MDA and a decrease in the serum glutathione level. While the administration of honey in combination with amikacin reduced the nephro-toxic effect of amikacin that represented by a reduction of the serum creatinine and urea, MDA and elevation of glutathione levels with improvement of the kidney histological findings in comparison with group 2.This study concluded that, honey decreased nephrotoxicity induced by amikacin through interference with the oxidative stress process, i.e. honey acts as free radical scavenger. Key words:amikacin, honey, nephrotoxicity, oxidative stress.

INTRODUCTION The increasing in the epidemic of obesity has been associated with doubling in the incidence of diabetes mellitus over the last 30 years especially in those with body mass index (BMI) ≥30 kg/m 2 , underscoring the close linking between obesity and metabolic syndrome. 1 Visceral adipose tissue secretes a variety of bioactive substances that might ABSTRACT Background: Insulin resistance impairs nitric oxide (NO) bioavailability; obesity promotes a state of metabolic syndrome and damages the vascular endothelium by altering lipid profile. Phosphodiesterase-5 (PDE-5) inhibitors restore NO signaling may improve metabolic parameters through a number of mechanisms. We hypothesized that daily administration of the PDE-5 inhibitor; sildenafil will improve fasting plasma glucose (FPG), triglyceride (TG) levels and body weight, in obese diabetic patients. Methods: Totally, 25 obese diabetic male patients with metabolic syndrome treated with sildenafil 25 mg daily for 3 months. Body weight, FPG levels, and lipid profile were determined monthly. Results: Treatment with sildenafil caused a reduction in fasting glucose levels, fasting TGs, cholesterol, low-density lipoprotein (LDL), very-LDL and increased high-density lipoprotein; body weight was significantly reduced. Conclusion: We have provided the first evidence that sildenafil therapy improve glycemic control, lipid profile and body mass index in diabetic patients with metabolic syndrome.