Study on Synergistic Effect of Bromocriptine and Sitagliptin in Streptozotocin-induced Diabetic Rats

Abstract

Introduction: Diabetes mellitus is a potentially morbid condition with high prevalence worldwide. Restoration of euglycemia in type 2 diabetes mellitus is difficult to achieve due to its multifactorial pathogenesis and frequently requires multiple anti-diabetic medications with different mechanism of action. This study is based on the possible synergistic effect of Sitagliptin and Bromocriptine in reducing blood sugar in diabetic animal models. Aim: To evaluate the effect of Sitagliptin and Bromocriptinemonotherapy and their combination in three different doses on blood sugar, Lipid profile, Liver and renal parameters in diabetic albino Wistar rats. Materials and Methods: An experimental animal study was conducted on 48 adult male albino wistar rats for a period of one month (August 2014). Streptozotocin induced (40 mg/kg IP) diabetic rats were divided into six groups of eight animals each weighing 150-200 gms. Group I- Vehicle (distilled water), Group II- Sitagliptin (100 mg/kg), Group III- Bromocriptine (10 mg/kg), Group IV- Sitagliptin (75 mg/kg) + Bromocriptine (7.5 mg/kg), Group V- Sitagliptin (100 mg/kg) + Bromocriptine (10 mg/kg), Group VI- Sitagliptin (125 mg/kg) + Bromocriptine (12.5 mg/kg). All drugs were given once daily (p.o) for four weeks. Body weight, fasting blood sugar, fasting lipid profile, liver parameters and renal parameters were estimated before and after administration of the drugs. Results were analyzed with SPSS software version 16.0 using one-way ANOVA followed by post-hoc Dunnett t test. P<0.05 was considered statistically significant. Results: The low dose combination therapy [Sitagliptin (75 mg/kg) + Bromocriptine (7.5 mg/kg)] showed a significant decrease in body weight (p<0.05), fasting blood sugar (p<0.001) compared with the vehicle group. It also showed a favorable lipid profile, renal and liver parameters compared with the vehicle, monotherapy and other combination regimens. Conclusion: The low dose combination therapy of Sitagliptin and Bromocriptine showed a better control over fasting blood sugar along with a beneficial effect on lipid profile, liver parameters and renal parameters than compared to other groups.

Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms

“…Group II (ST): Nondiabetic rats received ST (100 mg/kg) [26] dissolved in saline by oral gavage for 90 days.…”

“…GLP-1 is a hormone released from L-cells in the intestine that increases insulin secretion to regulate the circulating level of glucose. Ghorpade et al reported that the secretion of DPP4 from hepatocytes triggered adipose tissue inflammation and insulin resistance, while silencing of DPP4 reduced them; however, this effect was not produced with ST, indicating a diverse mode of action [24] Previous studies reported the hepatoprotective activity of ST in a mouse model of steatohepatitis via modulation of oxidative stress, lipid metabolism, and inflammatory mediators [25,26]. Besides that, new evidence suggested the protective effect of ST through the modulation of Nrf2 and NF-κB signaling pathways with subsequent suppression of inflammatory and apoptotic processes in methotrexate toxicity [27].…”