Bone-Marrow-Derived Mesenchymal Stem Cells, Their Conditioned Media, and Olive Leaf Extract Protect against Cisplatin-Induced Toxicity by Alleviating Oxidative Stress, Inflammation, and Apoptosis in Rats

Abstract

Background: Hepatic and renal damage is a cisplatin (Cis)-induced deleterious effect that is a major limiting factor in clinical chemotherapy. Objectives: The current study was designed to investigate the influence of pretreatment with olive leaf extract (OLE), bone-marrow-derived mesenchymal stem cells (BM-MSC), and their conditioned media (CM-MSC) against genotoxicity, nephrotoxicity, hepatotoxicity, and immunotoxicity induced by cisplatin in rats. Methods: The rats were randomly divided into six groups (six rats each) as follows: Control; OLE group, treated with OLE; Cis group, treated with a single intraperitoneal dose of Cis (7 mg/kg bw); Cis + OLE group, treated with OLE and cisplatin; Cis + CM-MSC group, treated with BM-MSC conditioned media and Cis; and Cis + MSC group, treated with BM-MSC in addition to Cis. Results: Cis resulted in a significant deterioration in hepatic and renal functions and histological structures. Furthermore, it increased inflammatory markers (TNF-α, IL-6, and IL-1β) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content, total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activity in hepatic and renal tissues. Furthermore, apoptosis was evident in rat tissues. A significant increase in serum 8-hydroxy-2-deoxyguanosine (8-OH-dG), nitric oxide (NO) and lactate dehydrogenase (LDH), and a decrease in lysozyme activity were detected in Cis-treated rats. OLE, CM-MSC, and BM-MSC have significantly ameliorated Cis-induced deterioration in hepatic and renal structure and function and improved oxidative stress and inflammatory markers, with preference to BM-MSC. Moreover, apoptosis was significantly inhibited, evident from the decreased expression of Bax and caspase-3 genes and upregulation of Bcl-2 proteins in protective groups as compared to Cis group. Conclusions: These findings indicate that BM-MSC, CM-MSC, and OLE have beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the hepatotoxicity, nephrotoxicity, immunotoxicity, and genotoxicity in a rat model.

A review of important heavy metals toxicity with special emphasis on nephrotoxicity and its management in cattle

“…Pb exposure causes histopathological alterations in the renal proximal tubular epithelium, which result in interstitial nephritis typically associated with hypertension ( 128 , 129 ). Pb gets collected in the renal cortex's proximal involuted tubules, which exhibit morphological and biochemical signs of Pb toxicity ( 130 ). Occult Pb nephropathy may not be detected as such because acute Pb-induced kidney damage can happen without acute overdose ( 131 ).…”

Platelet Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Mitigate Methotrexate-Induced Nephrotoxicity in Rat via Nrf2/Pparγ/HO-1 and NF-Κb/Keap1/Caspase-3 Signaling Pathways: Oxidative Stress and Apoptosis Interplay

“…Mesenchymal stem cells (MSCs) isolated from a variety of adult tissues have the capability to differentiate into multiple cell lineages [22,23]. MSCs have immunomodulatory, anti-inflammatory, anti-proliferative, reparative, and regenerative effects [22,24]. The regenerative capacity is due to paracrine effects mediated by the secretion of cytokines, growth factors, microvesicles, and exosomes for cell-to-cell communication with the injured renal cells [25].…”

Hepatoprotective effect of flaxseed oil and alpha lipoic acid against cisplatin-induced oxidative stress and apoptosis in rats

“…Cells undergo cell arrest and apoptosis in response to excessive ROS (Anbar et al, 2022). Numerous studies have documented liver damage carried on by CP (Elkomy et al, 2020;Elsayed et al, 2021;Aboraya et al, 2022;Anbar et al, 2022;Ibrahim et al, 2022). Also CP induced toxicity in different organs as kidney, testes and heart (Sallam et al, 2021;Elsayed et al, 2022).…”