ABSTRACT
Objective: Telmisartan is an angiotensin receptor blocker (ARB) that specifically blocks angiotensin II type-1 receptors (AT1R). Telmisartan has been proven to have antidiabetic effects via a variety of mechanisms, and it can be utilized in some diabetic patients due to its dual benefit for hypertensive patients with type 2 DM (T2DM) and when the other oral antidiabetic medications are intolerable or contraindicated. However, its precise underlying hypoglycemic mechanism is still obscure. Aim of work: We sought to establish a link between telmisartan administration and myostatin expression in skeletal muscles of T2DM rat model as a potential hypoglycemic mechanism of telmisartan. Materials and Methods: 32 male albino rats were included in the study; 8 rats served as controls (group I). T2DM was inducted in the other 24 rats, which were then randomly subdivided into 3 groups (8 in each): (group II) the Diabetic group and (groups III and IV) which were treated with either telmisartan (8 mg/kg/day) or metformin (250 mg/kg/day) respectively via oral gavage for a 4-week period. Results: Telmisartan administration resulted in a significant improvement in OGTT, HOMA-IR, glucose uptake, and muscle mass/body ratios in Telmisartan group as compared to Diabetic group (p < 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-α and IL-6 levels in Telmisartan group compared to diabetic rats (p < 0.05). Moreover, telmisartan significantly boosted SOD and GSH, and decreased MDA levels in the skeletal muscles of telmisartan group. Furthermore, a significant downregulation of myostatin and upregulation of insulin receptor, IRS-1, and IRS-3 genes in the skeletal muscles of Telmisartan group were also detected. Histologically, telmisartan attenuated the morphological damage in the skeletal muscle fibers compared to diabetic rats, as evidenced by a considerable decrease in the collagen deposition area percentage and a reduction in NF-kB expression in the muscle tissues of group III. Conclusion: Telmisartan administration dramatically reduced myostatin and NF-kB expressions in skeletal muscles, which improved insulin resistance and glucose uptake in these muscles, highlighting a novel antidiabetic mechanism of telmisartan in treating T2DM.
ABSTRACT
Background: Nickel oxide nanoparticles (NiO-NPs) have recently been utilized in various advanced industrial fields like lithium-ion micro batteries, nanofibers, electrochromic devices, and several biomedical applications. NiO-NPs are classified as extremely toxic substances as they can cause long-term harm to the environment and aquatic life. Moreover, frequent and prolonged exposure can affect human and animal health, causing skin allergies and major toxic consequences, such as hepatorenal toxicity. Hesperidin (HSP) has been proven to possess anti-inflammatory, antioxidant, and free radical scavenging activities. Objective: This study aimed to investigate the underlying protective mechanisms and effects of HSP against NiO-NPs-induced hepatorenal toxicities in rats. Materials and Methods: Forty male Wistar rats were randomly divided into four groups (n = 10 in each). The first group served as a Control group. For 8 weeks, the second group was administered NiO-NPs (100 mg/kg/day), and the third group was given HSP (100 mg/kg/day) via oral gavage for both groups. The fourth group received NiO-NPs and HSP concurrently in the same oral daily doses and duration as the second and third groups. Results: NiO-NPs administration revealed a significant increase in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (ALT, AST) in NiO-NPs group compared to Control group (p < 0.05). In addition, NiO-NPs administration resulted in a substantial increase in malondialdehyde levels with a significant drop in catalase activity and GSH content in Group II. Also, a significant decreased expression of Nrf-2 and Bcl-2 mRNA levels and upregulation of TNF-α, NF-kß and BAX in the liver and kidney of NiO-NPs group were also detected. Histologically, the liver and kidney of rats of NiO-NPs group showed significant histopathological disturbances, with a substantial increase in the proliferating cell nuclear antigen (PCNA) positive hepatocytes and renal tubular cells in the NiO-NPs group compared to Control and HSP groups (p < 0.05). In contrast, concomitant administration of HSP with NiO-NPs in group IV showed a significant biochemical, histopathological, and immunohistochemical improvement compared to NiO-NPs group. Conclusion: Co-administration of HSP with NiO-NPs significantly ameliorated most of the NiO-NPs-induced hepatorenal toxicities in male 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-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: Diabetic erectile dysfunction (DED) is a significant consequence of diabetes mellitus, and it is a multifactorial phenomenon that has no definitive treatment until now. Many therapeutic options provide symptomatic improvement rather than addressing the underlying etiology or restoring normal function. Stem cell (SC) therapy represents a potential hope in DED management. It is well established that the regenerative effect of stem cells can be attained by their paracrine action and their ability to differentiate into many cell lineages, including endothelial and smooth muscle cells. Hence, we tried to compare the effects of transplantation of urine-derived stem cells (USCs) or their lysate (USC-L) into the corpora cavernosa (CCs) of rats with DED. Materials and Methods: A total of 55 adult male Wistar rats were included in this study. USCs were obtained from ten healthy rats. Another ten rats did not subject to any intervention and served as a control (group I). Type 2 DM and DED were induced in the remaining 35 rats, but DED was tested and proved in only 24 rats, which were randomly divided into three groups (n = 8 in each). The DED group (group II) and either USCs (2 × 106 cells) or their lysate (200 µl) were transplanted into the CCs of each rat in the other two groups (groups III and IV), respectively. Results: Although the DED rats exhibited deterioration in all copulatory functions as compared to the control group, our histopathological, immunohistochemical, and morphometric results revealed that both USCs and USC-L have significantly restored the cavernous spaces, the ultrastructures of the endothelium that line the cavernous spaces, collagen/smooth muscle ratio, and the mean area percentage of α-SMA in the CCs as compared to DED rats. A respectable number of USCs was detected in the CCs of group III at the 4th week after transplantation, but this number significantly declined by the 8th week. Conclusion: Both USCs and USC-L can repair the structure and ultrastructure of CCs and improve the copulatory functions in the DED rat model. However, USC-L could be better used in DED to guard against the strange behavior of USCs after transplantation and their decreased survivability with time.
ABSTRACT
Cisplatin is an important antineoplastic drug used in multiple chemotherapeutic regimens but unfortunately causes serious toxic effects as ovarian and uterine toxicity. This study aimed to investigate the potential protective effect of resveratrol (RSV) against cisplatin-induced ovarian and uterine toxicity in female rats. Thirty-two female Wistar rats were divided randomly into four groups (n = 8 in each). Control group received oral normal saline for 28 days; RSV group received RSV (10 mg/kg; daily) via oral gavage; CIS group received a single dose of CIS (7 mg/kg; i.p.) on the 21st day; (CIS + RSV) group received both RSV and CIS by the same schedules and doses of RSV and CIS groups, respectively. Results demonstrated a significant decrease in MDA level and a significant increase in both glutathione content and activity of the antioxidant enzymes GPx, SOD, and CAT in the tissues of the ovary and uterus of CIS + RSV group in comparison to that of CIS group (P<0.05), also there are significantly decreased tissue levels of the proinflammatory cytokines and enzymes (NF-κB, IL-1ß, IL-6, TNF-α, COX-2, and iNOS), increased estradiol, progesterone, prolactin and decreased FSH serum levels in CIS + RSV group compared to CIS group (P < 0.05). Moreover, there is downregulation of tissues Cleaved Caspase-3, NF-κB and Cox-2 proteins as shown in Western blot analysis, also apoptosis was significantly inhibited, evidenced by downregulation of Bax and upregulation of Bcl-2 proteins, and the ovarian and uterine histological architecture and integrity were maintained in CIS + RSV group compared to CIS group. In conclusion, these findings indicate that RSV has beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the ovarian and uterine tissues of female rats.
