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

Abstract

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-1β, 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.

Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries

“…For instance, El-Demerdash et al found that LT attenuates carbon tetrachlorideinduced liver fibrosis and oxidative stress [36]. Moreover, LT markedly lowered diabetic associated oxidative hepatic damages in rats in another study [37]. Likewise, we reported that LT treatment corrects the altered redox status and oxidative injuries in liver tissues of hypercholesteremic animals.…”

Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model

“…Experimental diabetes was induced by a single intraperitoneal injection of 60 mg/kg freshly prepared streptozotocin (STZ; Sigma-Aldrich, ST. Louis, MO, USA) in 0.1 mol/L citrate buffer (pH 4.5), while control animals received equal volume of plain citrate buffer [ 12 ]. 72 hr following STZ injection, DM was verified by estimation of fasting blood glucose levels from animal's tail vein using Accu-Check Compact-Plus glucose meter system (Roche Diagnostics, Meylan, France) [ 13 ].…”

LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

“…Diabetes mellitus was induced by a single intraperitoneal injection (60 mg/kg) of streptozotocin (STZ) in overnight fasted rats by dissolving it in freshly prepared 0.1 M citrate buffer, pH 4.5 as previously described (Alotaibi et al, 2019). After STZ injection, the rats received free access of dextrose solution (5%) for 24 h to avoid hypoglycemic shock.…”