SALUBRIOUS EFFECT OF ROTTLERIN ON HYPEROXALURIA INDUCED OXIDATIVE DAMAGE IN RATS

Objective: To investigate the in vitro oxidant scavenging properties of rottlerin and to study the potential role of rottlerin on ethylene glycol induced nephrocalcinosis in rats.Methods: In vitro oxidant scavenging properties of rottlerin were studied along with its effect on in vitro calcium phosphate mineralization. For the in vivo studies, hyperoxaluria was induced by administering 0.4 % ethylene glycol and 1 % ammonium chloride in drinking water to male wistar rats for 9 d. Rottlerin was administered intraperitoneally at 1mg/kg/d along with the hyperoxaluric agent. Total thiols content, activities of glutathione-S-transferase (GST), glutathione reductase (GR), Citrate synthase (CS), isocitrate dehydrogenase (ICDH), ATPase and urinary parameters were studied.Results: Rottlerin showed in vitro DPPH, superoxide, and ABTS radical scavenging activity along with inhibition of calcium phosphate mineralization in an in vitro homogeneous system. The diminished activities of GST, GR, ICDH, CS, ATPase and level of total thiols were considerably stabilized by rottlerin, suggesting that rottlerin provides protection against oxalate induced oxidative damage.Conclusion: We suggest that rottlerin protects the integrity of the renal cell by stabilizing the free-radical mediated damage. Thus, the present study reveals that the antioxidant nature of rottlerin protects the renal cells against oxalate-induced injury and thus, rottlerin may prevent against hyperoxaluria induced oxidative damage.Keywords: Rottlerin, Hyperoxaluria, Oxidative stress, Antioxidan

A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada

Biliary tract cancers (BTC) are rare and aggressive tumors with poor prognosis. Radical surgery offers the best chance for cure; however, most patients present with unresectable disease, and among those receiving curative-intent surgery, recurrence rates remain high. While other locoregional therapies for unresectable disease may be considered, only select patients may be eligible. Consequently, systemic therapy plays a significant role in the treatment of BTC. In the adjuvant setting, capecitabine is recommended following curative-intent resection. In the neoadjuvant setting, systemic therapy has mostly been explored for downstaging in borderline resectable tumours, although evidence for its routine use is lacking. For advanced unresectable or metastatic disease, gemcitabine-cisplatin plus durvalumab has become the standard of care, while the addition of pembrolizumab to gemcitabine-cisplatin has also recently demonstrated improved survival compared to chemotherapy alone. Following progression on gemcitabine-cisplatin, several chemotherapy combinations and biomarker-driven targeted agents have been explored. However, the optimum regimen remains unclear, and access to targeted agents remains challenging in Canada. Overall, this article serves as a practical guide for the systemic treatment of BTC in Canada, providing valuable insights into the current and future treatment landscape for this challenging disease