engleski

Comparative effects of metformin and liraglutide on connexin 45 expression in kidneys of rats fed high-fat-high-sugar diet

Introduction: The aim of this research was to determine the localization and to quantify expression of connexin 45 (Cx45) in renal tissues from adult obese Sprague-Dawley rats fed high-fat- high-sugar diet and treated with two commonly used antidiabetic drugs metformin or liraglutide. Methods: 44 weeks old male and female Sprague- Dawley rats were separated in 4 groups: 1. Standard diet (SD), 2. High-fat high-sugar diet (HFHSD), 3. HFHSD + metformin (s.c., 50 mg/kg/day), 4. HFHSD + liraglutide (s.c., 0.3 mg/kg/day). The induction of obesity lasted for 6 weeks (groups 2, 3, and 4). A treatment (with metformin/liraglutide/no treatment) that followed lasted for 14 weeks. Renal tissue was collected and processed for plain histology and immunohistochemistry in order to quantify Cx45 expression. Results: Thickening of the Bowman’s capsule (BC) followed HFHSD treatment, but it was not ameliorated by metformin or liraglutide in both, male or female rats (P<0.01-P<0.001). Moreover, treatment with metformin in male animals resulted in even more thickening of the BC (P<0.001). Glomerular damage score was not changed in male animals, but in female animals it was the lowest in group treated with liraglutide (P<0.05- P<0.001). Expression of Cx45 in female animals was the highest in group 4 (P<0.05 vs. 1 and 2) while in male rats it was the highest in group 3 (P<0.05 vs. 1). Discussion and conclusion: There is sex dependent response in kidneys of HFHSD fed rats on treatment with metformin or liraglutide. That is consistent with growing number of data supporting sex-specific effects of both of these drugs. Both of them failed to ameliorate observed thickening of the BC caused by HFHSD treatment. Moreover, metformin even worsened it. However, glomeruli in kidneys from female animals treated with liraglutide were even in better condition in comparison with normally fed rats. This could be attributed to the amelioration of normal aging changes by liraglutide in these animals. Both of the drugs used are changing Cx45 expression in sex- and drug- dependent manner, pointing out that their effects in kidney could be related with amelioration of disruptions of gap junction- mediated intercellular communication.

chronic kidney disease ; high-fat-high sugar diet ; metformin ; liraglutide ; connexins

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