Reno-Hepatoprotective effects of Bryophyllum pinnatum against Hepatic Ischemia- Reperfusion Injury in male Wistar rats

Abstract Hepatic ischemia-reperfusion injury (HIRI) is indicated in postoperative complications in hepatic transplantation and surgeries. HIRI can lead to remote renal injury through systemic inflammatory and oxidative cascades. While current therapeutic options are effective, their potential toxic effects can pose additional challenges, thereby hindering hepatic and renal recovery, and highlighting the need for alternative therapies. Bryophyllum pinnatum (BP), popularly called “life plant” is widely used in traditional medicine, and is rich in flavonoids, triterpenoids, and bufadienolides, which have shown remarkable antioxidant and anti-inflammatory activities in various animal models. Studies have demonstrated the ability of BP to scavenge free radicals, suppress acute inflammation, and inhibit pro-inflammatory cytokines. Its nephroprotective effects in renal injury models, as well as its hepatoprotective effects in chemically-induced hepatocarcinogenesis have also been documented. Despite these promising findings, its effect against HIRI-induced kidney damage remains unexplored. This study investigates the reno-hepatoprotective potential of BP methanolic leaf extract in male Wistar rats subjected to HIRI. Forty male Wistar rats were divided into four groups (n=10); group 1- Sham operated, group 2-HIRI, group 3-LDH (low-dose B. pinnatum (100 mg/kg), group 4-HDH (high-dose B. pinnatum (200 mg/kg). BP was administered orally via gavage for 14 days before HIRI induction. Following treatment, animals were anesthetized with ketamine (50 mg/kg) and xylazine (10 mg/kg), and HIRI was induced by clamping the hepatic artery, portal vein and bile duct for 60 minutes to induce ischemia after which the clamp was removed for hepatic reperfusion which lasted for 24-hours. Animals were euthanized under deep anesthesia (ketamine 50 mg/kg and xylazine 10 mg/kg, ip) before sacrifice. Then, blood, kidney and liver tissues were harvested for biochemical and histological analysis. Data were analyzed using one way ANOVA with Graph pad prism. Tukey’s post-hoc test was used for multiple comparison. P<0.05 was considered statistically significant. Biochemical analyses showed a significant restoration in SOD, catalase, and GSH levels and reductions in MDA and inflammatory markers (TNF-α, MPO) in the B. pinnatum groups. In addition, altered ALT, ALP, and GGT levels were restored, and urea and creatine levels raised as a secondary effect of HIRI were reduced in the B. pinnatum-treated groups. Reduced caspase-3 activity was also observed in B. pinnatum-treated groups, indicating lower apoptosis levels. Histological analyses showed improved cytoarchitecture, with preservation of renal corpuscles and reduced inflammation. Conclusively, B. pinnatum exhibits reno-hepatoprotective effects on HIRI-induced kidney damage, potentially modulating oxidative stress, inflammation, and apoptotic pathways.