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Updated: Jul 7, 2026
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
G protein-coupled estrogen receptor activation attenuates cisplatin-induced CKD in C57BL/6 mice: An insight into
Hala A Ahmed1, Ahmed A Shaaban2, Tarek M Ibrahim2
1Pharmacology and Biochemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt.
Abstract:
Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) post-cisplatin therapy. This study aims at investigating the potential effect of G1 compound, a GPER agonist, on attenuating cisplatin-induced CKD. To induce CKD in male, intact female, and ovariectomized (OVX) mice, CKD was induced by injecting two cycles of 2.5 mg/kg cisplatin with a 16-day recovery period between cycles). G1 (50 or 100 μg/kg was administered daily for 6 weeks. Severity of renal damage was more pronounced in males than females. Interestingly, OVX resulted in renal damage that is non-significant compared to males and significantly higher than females. G1 improved renal function and blood flow as evidenced by reduction of serum creatinine and elevation of creatinine clearance, NO production, and reduction of ET1. This renoprotective effect could be attributed to its immunomodulatory effect regulated by TGF-β that shifted the balance to favor anti-inflammatory cytokine production (increased IL-10) rather than pro-inflammatory cytokines (decreased Th17 expression). Reduction of TGF-β activation also inhibited epithelial-to-mesenchymal transition that eventually ameliorated CKD development. Antioxidant potential of G1 has been demonstrated by upregulation of Nrf2 and subsequent antioxidant enzymes. These data suggest that G1 could be a promising therapeutic tool to attenuate CP-induced CKD.
Insights
G1 compound, a GPER agonist, shows promise in protecting against cisplatin-induced kidney damage by reducing inflammation and oxidative stress, offering a potential therapeutic strategy for chronic kidney disease (CKD).
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Chronic kidney disease (CKD) incidence and progression differ between genders following cisplatin chemotherapy.
- Cisplatin, a common chemotherapy agent, can induce significant kidney damage (nephrotoxicity).
- Estrogen receptor pathways may influence kidney disease outcomes.
Purpose of the Study:
- To investigate the renoprotective effects of G1, a GPER agonist, against cisplatin-induced CKD.
- To explore the impact of gender and ovariectomy on cisplatin-induced kidney injury.
- To elucidate the mechanisms underlying G1's potential therapeutic actions.
Main Methods:
- CKD was induced in male, female, and ovariectomized (OVX) mice using cisplatin injections.
- Mice were treated with G1 (50 or 100 μg/kg) daily for six weeks.
- Renal function, blood flow markers, inflammatory cytokines, epithelial-to-mesenchymal transition (EMT), and antioxidant pathways were assessed.
Main Results:
- Renal damage was more severe in male and OVX mice compared to intact females.
- G1 treatment significantly improved renal function, evidenced by reduced serum creatinine and increased creatinine clearance.
- G1 demonstrated immunomodulatory effects (reduced Th17, increased IL-10), inhibited EMT, and enhanced antioxidant defense (Nrf2 upregulation).
Conclusions:
- G1 exhibits significant renoprotective effects against cisplatin-induced CKD in a gender-dependent manner.
- The protective mechanisms involve reducing inflammation, inhibiting EMT, and boosting antioxidant capacity.
- G1 represents a potential therapeutic candidate for mitigating chemotherapy-induced kidney damage.
