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-1ß) 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.
ABSTRACT
BACKGROUND: Osteoarthritis (OA) is a chronic degenerative debilitating disease, primarily affects joints, particularly weight-bearing areas. The surface layer of the articular cartilage breaks down and wears away leading to rubbing of bones, pain, swelling, and joint stiffness. AIM AND OBJECTIVES: This study investigates the possible therapeutic effects of intra-articular versus intravenous injection of umbilical cord blood mesenchymal stem cells (UCB-MSCs) against mono-iodoacetate-induced OA of the knee joints in male albino rats, using histological and immunohistochemical techniques. MATERIALS AND METHODS: Thirty male adult albino rats were randomized into five groups as follows: Group (I) and (II): Served as control. Group (III): Osteoarthritic group. Group IV: Osteoarthritic and intraarticularly-injected MSCs. Group V: Osteoarthritic and intravenously-injected MSCs. Animals were sacrificed 1 month after stem cell injection, the right knee was prepared for histological techniques (Hematoxylin and Eosin and Toluidine blue stains) and immunohistochemical technique (Bax stain). Prussian blue stain was used to assess homing of MSCs in Groups IV and V. RESULTS: Knee joint surface was irregular, fissured, and fragmented in Group III. In Groups IV and V, affected area was filled with newly formed tissue. Toluidine blue showed a decrease in matrix staining in Group III compared to both control and MSCs-treated groups. Chondrocytes in Group III showed strong Bax immunoreactivity and this reaction decreased in Group IV and V; however, Group V immunoreactivity was more than Group IV. Prussian blue stain showed labeled UCB-MSCs in many chondrocytes in Group IV and few chondrocytes in Group V. CONCLUSION: Intraarticularly-injected UCB-MSCs showed better healing of knee OA than intravenously-injected UCB-MSCs.
