The present study was designed to evaluate the possible synergistic effects of telmisartan and quercetin in 5 fluorouracil (5-FU) induced nephrotoxicity in rats. Methodology: Forty male rats were randomly divided into five groups: The negative control group, the positive control group that received 5-FU, the telmisartan group, receiving 10 mg/kg, the quercetin group, receiving 80 mg/kg, and the combination of telmisartan and quercetin group. All the treatments were given orally for 14 days. A single intraperitoneal injection of 5-FU (150 mg/kg) on day 13 of the experiment was given except for the negative control group. On the 15th day after scarification, approximately 5 mL of blood was collected and used for measurement of CBC, urea, creatinine, and uric acid. The kidneys were used for histopathological examination and for the measurement of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (Cys-C), and total antioxidant capacity (TAOC). Results: The combination therapy significantly attenuated the levels of tissue KIM-1, NGAL, Cys-C, and serum uric acid as well as blood inflammatory markers, Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR), and Platelets/Lymphocyte ratios (PLR), and restored the TAOC. The histopathological findings greatly support the biochemical tests. Conclusion:The results strongly suggest the renoprotective effects of telmisartan and quercetin in combination against the nephrotoxic effect of 5-FU through decreasing the levels of KIM-1, NGAL, and cys-C, and the novel inflammatory markers of kidney injury like NLP, MLR, and PLR, as well as decreasing uric acid and restoring the TAOC. The proposed mechanism could be the additive inhibitory effect on RAS provided by both telmisartan and quercetin.

Tenofovir is a reverse-transcriptase inhibitor based on acyclic nucleotide analogs. Tenofovir is a drug that is often used in treating HIV infection and has also been approved for treating infection by the hepatitis B virus. Despite the fact that its renal safety has been demonstrated in cell culture and clinical trials, clinical use and in vivo animal studies have shown its association with a low, but important, risk of kidney injury. Tenofovir accumulation in these mitochondria-rich cells is explained by proximal tubular cell secretion. Proximal tubular cell dysfunction is a symptom of Tenofovir nephrotoxicity, which might be the leading cause of acute renal injury or chronic diseases of the kidney. A review of articles is performed using keywords related to the topic in the databases of Google Scholar and PubMed, and 54 papers have been included, which were case studies, cross-sectional studies, and in vivo animal studies from 2004 up to 2021. The review aims at explaining the interaction of Tenofovir with kidney tubules, an association of genetic polymorphism, clinical features of Tenofovir-induced renal toxicity, potential mechanisms of Tenofovir-induced renal toxicity, its predisposing conditions and factors, and finally, some proposed strategies and agents to monitor and manage Tenofovir-induced nephrotoxicity.

Diabetes mellitus (DM) with uncontrolled blood sugar causes a variety of problems, including coronary artery disease, stroke, heart failure, hypertension, nephropathy, neuropathy, and retinopathy. These consequences harm the diabetic patients' lives. Many studies have shown that diabetic patients have a higher rate of heart failure and a worse prognosis than non-diabetic people. Sodium and glucose co-transporter receptor-2 (SGLT2) inhibitors are a relatively new class of anti-diabetic drugs. They not only regulate blood sugar but also have positive cardiovascular effects via a variety of mechanisms. This review intends to show that SGLT2 inhibitors, in addition to good glycemic control, possess a cardioprotective role. We conducted a literature review and identified 20 adequately powered clinical trials and animal studies in type 2 DM that investigated the cardiovascular (CV) effects of SGLT2 inhibitors (particularly heart failure and hypertension). These studies looked at the cardiovascular effects of three SGLT2 inhibitors: Empagliflozin, Canagliflozin, and Dapagliflozin. In diabetic patients, these three inhibitors of SGLT2 significantly lowered the risk of heart failure and hypertension, making them valuable therapy for lowering CV risks in high cardiovascular-risk individuals with T2DM. Finally, the use of SGLT2 inhibitors in patients without diabetes mellitus showed positive metabolic outcomes in weight and blood pressure control.