Insulin resistance (IR) has emerged as one of the main risk factors for renal fibrosis (RF) that represents a common stage in almost all chronic kidney disease. The present study aims to investigate the inhibitory effect of empagliflozin (EMPA "a sodium-glucose co-transporter 2 inhibitor") and infliximab [IFX "a tumor necrosis factor-α (TNF-α) antibody"] on RF in rats with induced IR. IR was induced by adding 10% fructose in drinking water for 20 weeks. Thereafter, fructose-induced IR rats were concurrently treated with EMPA (30 mg/kg), IFX (1 dose 5 mg/kg), or EMPA + IFX for 4 weeks, in addition to IR control group (received 10% fructose in water) and normal control (NC) group. Rats with IR displayed hyperglycemia, deterioration in kidney functions, glomerulosclerosis, and collagen fiber deposition in renal tissues as compared to NC. This was associated with downregulation of the renal sirtuin 1 (Sirt 1) expression along with higher renal tissue TNF-α and transforming growth factor-β1 (TGF-β1) levels. Both EMPA and IFX significantly modulated the aforementioned fibrotic cytokines, upregulated the renal Sirt 1 expression, and attenuated RF compared to IR control group. Of note, IFX effect was superior to that of EMPA. However, the combination of EMPA and IFX alleviated RF to a greater extent surpassing the monotherapy. This may be attributed to the further upregulation of renal Sirt 1 in addition to the downregulation of fibrotic cytokines. These findings suggest that the combination of EMPA and IFX offers additional benefits and may represent a promising therapeutic option for RF.

Tramadol represents a synthetic opioid analgesic especially for mild to severe pain. Its dose must be commonly monitored according to pain status and to alleviate the appearance of any adverse effects such as renal cellular damage during its excretion. Present work aimed mainly to study the effects of tramadol intake on renal tissues and 10-dehydrogingerdione (10-DHGD) potential as a protective agent. Tramadol administration induced an increase in serum levels of urea, creatinine, uric acid, the renal immune expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and caspase-3 which turned out to be decreased by 10-DHGD intake. Our results also recorded a significant increase in renal malondialdehyde (MDA), toll-like receptor 4 (TLR4), and extracellular signal-regulated protein kinase-1 (ERK1) along with glutathione (GSH), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) decrease due to tramadol intake, which were counteracted by 10-DHGD administration as illustrated and supported by the histopathological findings. Our conclusion refers to renoprotective potential of 10-DHGD against tramadol adverse effects.

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Sunitinib has been associated with several cardiotoxic effects such as cardiac fibrosis. The present study was designed to explore the role of interleukin (IL)-17 in sunitinib-induced myocardial fibrosis (MF) in rats and whether its neutralization and/or administration of black garlic (BG), a form of fermented raw garlic (Allium sativum L.), could extenuate this adverse effect. Male Wistar albino rats received sunitinib (25 mg/kg three times a week, orally) and were co-treated with secukinumab (3 mg/kg, subcutaneously, three times total) and/or BG (300 mg/kg/day, orally) for four weeks. Administration of sunitinib induced significant increase in cardiac index, cardiac inflammatory markers, and cardiac dysfunction that were ameliorated by both secukinumab and BG, and to a preferable extent, with the combined treatment. Histological examination revealed disruption in the myocardial architecture and interstitial fibrosis in cardiac sections of the sunitinib group, which were reversed by both secukinumab and BG treatments. Both drugs and their co-administration restored normal cardiac functions, downregulated cardiac inflammatory cytokines, mainly IL-17 and NF-κB, along with increasing the MMP1/TIMP1 ratio. Additionally, they attenuated sunitinib-induced upregulation of the OPG/RANK/RANKL axis. These findings highlight another new mechanism through which sunitinib can induce interstitial MF. The current results propose that neutralizing IL-17 by secukinumab and/or supplementation with BG can be a promising therapeutic approach for ameliorating sunitinib-induced MF.