Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats

Abstract

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.

Integrated blood and organ profile analysis to evaluate ameliorative effects of kaempferol on 5-fluorouracil-induced toxicity

“…Conversely, the DMH/KMP group exhibited increased infiltration of inflammatory cells, hinting at the protective role of KMP in kidney health. The DMH/5-FU(HD)/KMP group demonstrated mild glomerular degeneration, congestion, and tubular degeneration, implicating high-dose 5-FU treatment in renal damage 43 . Most intriguingly, the DMH/5-FU(LD)/KMP group showcased a normal renal morphology with no evidence of inflammation or necrosis, thereby highlighting a potentially less damaging response compared to the high-dose regimen.…”

Preclinical evidence of reno-protective effect of quercetin on acute kidney injury: a meta-analysis of animal studies

“…As shown in Figure 3A, quercetin pre-treatment significantly decreased the sCr in AKI (SMD: 2.73, 95% CI: 3.66, −1.80; p < 0.01; I 2 = 80%) (Chander et al, 2005;Kusumoto et al, 2011;Sanchez-Gonzalez et al, 2011;Nabavi et al, 2012;Chen et al, 2014;Saito et al, 2014;Li et al, 2016;Gholampour and Sadidi, 2018;Lucida et al, 2019;Tan et al, 2019;Tan et al, 2020;El-Sayed et al, 2021;Goncalves et al, 2021;Rahdar et al, 2021;Wang et al, 2020;Ali et al, 2022;Vazquez-Atanacio et al, 2022;Yilmaz et al, 2022). Furthermore, sensitivity analysis results showed no variation in the pooled estimate of sCr, suggesting that quercetin has a robust effect in reducing sCr in AKI animals (Figure 3B).…”

“…This meta-analysis included 18 research with 278 animals (Chander et al, 2005;Kusumoto et al, 2011;Sanchez-Gonzalez et al, 2011;Nabavi et al, 2012;Saito et al, 2014;Li et al, 2016;Gholampour and Sadidi, 2018;Shu et al, 2018;Tan et al, 2019;Tan et al, 2020;El-Sayed et al, 2021;Goncalves et al, 2021;Rahdar et al, 2021;Wang et al, 2020;Ali et al, 2022;Vazquez-Atanacio et al, 2022;Yilmaz et al, 2022). The result showed that quercetin administration obviously decreased BUN (SMD = −4.78; 95% CI: 6.45, −3.12; p < 0.01; I 2 = 84%) in AKI animals (Figure 2A).…”

“…After reading the full-text articles, 55 studies were excluded due to 1) the animal model not being correct, 2) data not being clear, 3) duplicate data, and 4) the original text not being available. Finally, 19 studies were eligible in which 288 animals were included (Chander et al, 2005;Kusumoto et al, 2011;Sanchez-Gonzalez et al, 2011;Nabavi et al, 2012;Chen et al, 2014;Saito et al, 2014;Li et al, 2016;Gholampour and Sadidi, 2018;Shu et al, 2018;Lucida et al, 2019;Tan et al, 2019;Tan et al, 2020;El-Sayed et al, 2021;Goncalves et al, 2021;Rahdar et al, 2021;Wang et al, 2020;Ali et al, 2022;Vazquez-Atanacio et al, 2022;Yilmaz et al, 2022) (Figure 1). Frontiers in Pharmacology frontiersin.org Frontiers in Pharmacology frontiersin.org…”

New insights into the potential cardioprotective effects of telmisartan and nanoformulated extract of Spirulina platensis via regulation of oxidative stress, apoptosis, and autophagy in an experimental model

“…After 14 days of acclimatization, the animals were divided into nine groups (Gp) with six rats each as follows: Gp I (VC): intragastric administration of saline for 21 days; Gp II (PC): intragastric administration of chitosan polymer for 21 days; Gp III (TEL): intragastric administration of 10 mg/kg of telmisartan (TEL) for 21 days ( Ali et al, 2022 ); Gp IV (free Sp): intragastric administration of 300 mg/kg of free Sp extract for 21 days ( Khalil et al, 2020 ); Gp V (nano Sp): intragastric administration of 100 mg/kg of nano Sp extract for 21 days ( Hardiningtyas et al, 2022 ); Gp VI (Cyclo): one intraperitoneal injection of 200 mg/kg Cyclo on day 18 of the experiment ( Bhatt et al, 2017 ); Gp VII (TEL + Cyclo): intragastric administration of 10 mg/kg of TEL for 21 days plus one intraperitoneal injection of Cyclo (200 mg/kg) on day 18; Gp VIII (free Sp + Cyclo): intragastric administration of 300 mg/kg of free Sp extract for 21 days plus one intraperitoneal injection of Cyclo (200 mg/kg) on day 18; Gp IX (nano Sp + Cyclo): intragastric administration of 100 mg/kg of nano Sp extract for 21 days plus one intraperitoneal injection of Cyclo (200 mg/kg) on day 18.…”