In vivo Assessment of Combined Effects of Glibenclamide and Losartan in Diabetic Rats.

OBJECTIVE: Diabetic complications involve multiple pathological pathways, including hyperglycemia-induced oxidative stress and inflammation. Combination therapy is usually employed to improve treatment outcomes and to lower potential adverse effects. In this study, we evaluated the effects of antidiabetic and antihypertensive agents, glibenclamide (GLI) and losartan (LT), on diabetes mellitus (DM)-associated metabolic changes in rats. MATERIALS AND METHODS: Streptozotocin-induced diabetic animals were orally treated with GLI 5 mg/kg and/or LT 25 mg/kg for 4 weeks. Blood glucose, insulin, aspartate aminotransferase, alanine aminotransferase, urinary creatinine, and urea levels were measured. Serum, liver, and kidney values of inflammatory markers, such as interleukin-1ß, tumor necrosis factor alpha, and interleukin-6 were assessed, along with lipid peroxidation products (e.g., thiobarbituric acid reactive substances), endogenous antioxidants (e.g., glutathione), as well as antioxidant enzyme activities (e.g., catalase, superoxide dismutase, and glutathione peroxidase). Finally, histological changes in liver and kidney tissues were evaluated. RESULTS: DM markedly induced systemic, hepatic, and renal inflammation and lowered antioxidant defense mechanisms. Treatment of diabetic rats with either GLI or LT significantly improved liver and kidney functions and histological structure. Moreover, both medications reduced signs of oxidative stress and inflammation in blood, liver, and kidney samples. Combining GLI and LT showed similar protective potential against systemic, hepatic, and renal oxidative stress and inflammation. CONCLUSION: Adding LT to GLI therapy revealed prospective antioxidant and anti-inflammatory action, while no synergistic or additive effects were observed.

Garcinia mangostana extract and curcumin ameliorate oxidative stress, dyslipidemia, and hyperglycemia in high fat diet-induced obese Wistar albino rats.

The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into eight experimental groups, fed on a normal diet or high-fat diet (HFD), then given mangosteen extract (400 mg /kg /day) and/or curcumin (80 mg/kg /day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Mangosteen pericarp extract (MPE) induced a remarkable decrease in BMI (from 0.86 to 0.81 gm/cm2), while curcuma either alone or in combination was more effective, as treated rats recorded BMIs of 0.78 and 0.79 gm/cm2, respectively. Regarding the antioxidant effects, MPE induced a significant increase of GSH in obese rats (123.86 ± 15.53 µg/ml vs 288.72 ± 121.37 µg/ml). As anti-atherogenic agents MPE demonstrate significant effect recorded higher level of HDL-C in treated animals, but ineefective as anti-dyslipidemic agent. Curcumin was more effective in reducing LDL-C levels in obese rats. Both extracts effectively reduced blood glucose. The present study demonstrated that MPE and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.

High-fat diet-induced obesity and impairment of brain neurotransmitter pool.

Obesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.