The Protective Effects of Sesamin against Cyclophosphamide-Induced Nephrotoxicity through Modulation of Oxidative Stress, Inflammatory-Cytokines and Apoptosis in Rats

Abstract

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1β and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.

Oral delivery of nerolidol alleviates cyclophosphamide-induced renal inflammation, apoptosis, and fibrosis via modulation of NF-κB/cleaved caspase-3/TGF-β signaling molecules

“…( 2020 ), Alshahrani et al. ( 2022 ), and Bokhary et al. ( 2022 ); etc., have also shown increased expression of along with an increase in the level of TNF-α, IL-6, and IL-1β leading to renal inflammation and renal damage upon cyclophosphamide administration whereas these attributes were mitigated, when natural products such as sesamin, Cyclina sinensis , Salvadora persica, etc., were used (Jiang et al., 2020 ; Alshahrani et al., 2022 ; Bokhary et al., 2022 ).…”

“…( 2022 ) and Ghareeb et al. ( 2019 ) have also reported the significant oxidative stress caused by CP exposure and its mitigation when different natural products were used (Ghareeb et al., 2019 ; Jiang et al., 2020 ; Alshahrani et al., 2022 ).…”

“…( 2022 ), and Ijaz et al. ( 2022 ), have also shown increased renal apoptosis when exposed to cyclophosphamide, whereas treatment with natural products such as Sesamin, Picrorhiza Kurroa, Herbactin mitigated the renal apoptosis via modulation of caspase 3 levels (Sharma et al., 2017 ; Jiang et al., 2020 ; El-Shabrawy et al., 2020 ; Alshahrani et al., 2022 ; Ijaz et al., 2022 ). Considering these facts, we also estimated the effect of CP on the expression of caspase-3 using in vitro and in vivo studies.…”

Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management

“…The connection between Alkylating agents and hypertension remains unclear because they are usually used in combination with other drugs for cancer treatment [ 45 ]. Cyclophosphamide has a wide range of complications, such as nephrotoxicity, endothelial injury, and abnormalities in the renin-angiotensin system leading to hypertension [ 46 , 47 ]. While the mechanisms mentioned above could potentionally render Cyclophosphamide-associated Hypertension possible, it has not yet been recognized as an independent risk factor for hypertension in cancer patients.…”

“… Immune therapeutic agents Immune checkpoint inhibitors [ 39 , 40 , 99 ] • dysregulated NO hemostasis and vasoconstriction Bortezomib [ 38 ] Carfilzomib [ 38 ] Everolimus [ 35 ] Myocarditis [ 100 ] arrhythmias, conduction abnormalities [ 100 ] pericardial diseases [ 100 ] interstitial nephritis glomerulonephritis [ 99 , 101 ] Acute kidney injury [ 101 ] cardiotoxicity [ 102 – 104 ] mTOR inhibitors • increased oxidative stress [ 34 ] sympathetic activation [ 34 ] Rapamycin Hyperglycemia [ 105 ], hypercholesterolemia [ 105 ], hypertriglyceridemia [ 105 ] CAR-T therapy fever, flu-like symptoms, low blood pressure, and organ damage [ 106 ] Ubiquitin-proteasome inhibitors [ 39 , 40 , 99 ] • blocking the β proteolytic subunits of the 20s proteasome bortezomib and carfilzomib muscle weakness and tingling [ 107 ] Traditional chemotherapeutic agents Alkylating agents • creating cross-linkage in DNA strands and cell death [ 43 ] • disturbance in renin-angiotensin system [ 48 ]. Cyclophosphamide [ 46 , 47 ] ifosfamide [ 48 ] Anthracycline [ 49 ] Cisplatin [ 51 ]. Nephrotoxicity endothelial injury abnormalities in the renin-angiotensin system [ ...…”