Department of Pharmacy
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Item Phloretin as an add-on therapy to losartan attenuates diabetes-induced AKI in rats: A potential therapeutic approach targeting TLR4-induced inflammation(Elsevier, 2023-11) Gaikwad, Anil BhanudasTargeting Toll-like receptor 4 (TLR4) and Angiotensin II type 1 receptor (AT1R) could provide renoprotection during acute kidney injury (AKI) mainly by regulating inflammation, oxidative stress, mitochondrial dysfunction, and apoptosis. Phloretin (TLR4 inhibitor) as an add-on therapy to losartan (AT1R inhibitor) could provide more therapeutic benefits against AKI under diabetic condition. We aimed to study the effect of phloretin as an add-on therapy to losartan against AKI under diabetic condition.Item Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis(MDPI, 2023-10) Gaikwad, Anil BhanudasCalcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney’s filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations. Voclosporin (VOC), a novel CNI, no longer requires drug level monitoring and seems to lack these adverse effects, although hypertension and drug–drug interactions still occur. VOC demonstrated efficacy superior to standard-of-care in controlling active lupus nephritis in the phase 2 AURA-LV and the phase 3 AURORA-1 trials and was approved for the treatment of active lupus nephritis. However, how to implement VOC into the current and changing treatment landscape of lupus nephritis is still debated. Here, we review the unique chemistry, pharmacology, and toxicity profile of VOC, summarize the efficacy and safety data from the AURA-LV and AURORA-1 trials, and discuss the following four possible options to implement VOC into the management of lupus nephritis, namely regarding B cell-targeting therapy with belimumab (BEL). These include: 1. patient stratification to either VOC or BEL, 2. VOC/BEL combination therapy, 3. VOC-BEL sequential therapy, or 4. alternative options for the rapid antiproteinuric effect of VOC.Item Disparity in actions of rosiglitazone against cisplatin-induced nephrotoxicity in female Sprague-Dawley rats(Elsevier, 2013-11) Gaikwad, Anil BhanudasCisplatin is one of the most common chemotherapeutic drugs used against various solid, tumours. Despite of its therapeutic benefits, its use in clinical practice is often limited because of dose, related toxicity. The nephrotoxic potential of cisplatin has been ascribed to its accumulation in the, renal tubular cells generating reactive oxygen species (ROS), activation of Bax, increased secretion of, TNFα and activation of certain inflammatory mediators like cytokines. The present investigation was, undertaken with an objective to study the effect of rosiglitazone against cisplatin induced, nephrotoxicity. Pretreatment of rosiglitazone prevents cisplatin induced nephrotoxicity which was, clearly evident from the renal biochemical parameters like reduced BUN, creatinine and TNFα levels, and increased albumin levels, which was also supported by histopathological studies of the kidneys. In contrast, posttreatment of rosiglitazone was not able to protect the renal damage in cisplatin induced, renal toxicity. These results showed the variation of pre & posttreatment effects of rosiglitazone, against the cisplatin induced nephrotoxicity.