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Aminoglycoside nephrotoxicity stands as a primary contributor to the development of acute intrinsic renal failure. Distinctive characteristic associated with this nephrotoxicity is the occurrence of tubular necrosis, which is why it is commonly referred to as acute tubular necrosis. Studies have demonstrated that inhibiting rhoA/rho-kinase pathway is beneficial for kidney damage induced by diabetes and renal ischemia. Comparable pathological conditions can be observed in aminoglycoside nephrotoxicity, like those found in diabetes and renal ischemia. Gentamicin, an aminoglycoside, is known to activate Rho/Rho-kinase pathway. The primary goal of this study is to explore influence of oxidative stress on this pathway by concurrently administering gentamicin and alpha-linolenic acid (ALA) possessing known antioxidant properties. To achieve this, gentamicin (100 mg kg−1) and ALA (70 mg kg−1) were administered to mice for a period of 9 days, and Rho/Rho-kinase pathway was examined by using ELISA. Administration of gentamicin to mice led to an elevation in RhoA and rho-kinase II levels, along with the activity of rho-kinase in kidneys. However, ALA effectively reversed this heightened response. ALA, known for its antioxidant properties, inhibited activation of Rho/Rho-kinase pathway induced by gentamicin. This finding suggests that gentamicin induces nephrotoxicity through oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: The effect of Hypericum perforatum (HP), which is a medicinal plant, on sciatic nerve injury-induced peripheral neuropathy has been less studied so far. The current experimental study aimed to investigate the neuroprotective and antinociceptive effects of Hypericum perforatum (HP) extract on sciatic nerve injury-induced peripheral neuropathy in mice. Materials and Methods: In the present study, 18 Balb/C albino mice were allocated equally into three groups. The first group was determined as controls, and no procedure was performed on these mice. Neuropathy was generated by the partial sciatic nerve ligation method on mice allocated to the second and third groups. Mice in the third group received HP extract at a dose of 70 mg/kg per day for fourteen days. Nociception (cold allodynia) was evaluated using the cold plate test at the end of the experimental period. Tumor necrosis factor -alpha (TNF-a) and interleukin-6 (IL-6) in plasma; inducible nitric oxide synthase (iNOS), phospholipase A2, cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-αB), caspase-3, Bcl-2, and Bax levels in sciatic nerve were measured by enzyme-linked immunosorbent assay test. Results: Cold plate latencies (sec) of the neuropathy + HP, neuropathy, and control groups were 8.33 ± 0.67, 5.17 ± 0.60, and 13 ± 0.73, respectively. Plasma TNF-a, IL-6 levels, and sciatic nerve iNOS, COX-2, NF-αB, caspase-3, and Bax levels were significantly decreased after HP supplementation. Bcl-2 levels of the neuropathy + HP, neuropathy, and control groups were 9.92 ± 0.71, 5.37 ± 0.53, and 13.65 ± 0.68, respectively. Conclusion: HP has improved oxidative, inflammatory, and apoptotic responses, as well as cytokine levels in plasma and sciatic nerves of mice. It has been concluded that HP provided neuroprotective, anti-inflammatory, and antinociceptive effects in experimental mice with sciatic nerve injury models, which is suggested to guide future studies on neuropathic pain management. [ABSTRACT FROM AUTHOR]

This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an eight-week-old Balb\c albino strain were divided into four groups: control group, CsA group, DAPA group, and CsA + DAPA group. On day 9 of treatment, the animals were decapitated, and bilateral nephrectomy was performed. Oxidative stress and apoptosis were evaluated with caspase-3 activity, total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), myeloperoxidase (MPO), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the right kidney resection material. The left kidney resection material was evaluated histopathologically. CsA increased caspase-3 activity, Bax, TOS, MDA, TAS, and MPO levels, and the administration of DAPA with CsA significantly reduced this increase in levels (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). CsA decreased Bcl-2 levels, and administration of CsA + DAPA significantly increased Bcl-2 levels compared with only CsA administration (p < 0.001). Additionally, administration of DAPA significantly reduced the histopathological findings (parenchymal inflammation, hyaline cast formation, vacuolization, and lysis of renal tubular cells) caused by CsA. DAPA reduces oxidative stress, apoptosis, and histopathological damage caused by CsA in renal tissue. [ABSTRACT FROM AUTHOR]

Aim: The expression of the cognate receptor of advanced glycation end products (RAGE) in malignant tissues of patients with type 2 diabetes has been suggested as a co‐factor determining the clinical course and prognosis. We aimed to investigate the relationship between RAGE expression and clinicopathological features of prostate neoplasia. Methods: Tissue samples of 197 patients, 64 (24 patients with type 2 diabetes and 40 controls) with benign prostate hyperplasia (BPH) and 133 (71 patients with type 2 diabetes and 62 controls) with localised or metastatic prostate cancer (LPCa/MetPCa) were included in the study. The expression of RAGE in prostate specimens was studied immunohistochemically. RAGE scores were determined according to the extent of immunoreactivity and staining intensity. Results: RAGE expression in BPH group (patients with type 2 diabetes and controls) was negative. Patients with both LPCa and MetPCa had significantly higher scores than those with BPH (P <.001). The mean RAGE scores of patients with type 2 diabetes LPCa and MetPCa were 4.71 ± 3.14 and 4.97 ± 3.69. The mean scores of control LPCa and MetPCa were 1.52 ± 1.87 and 1.69 ± 1.58, respectively. The scores of patients with type 2 diabetes LPCa and MetPCa were significantly higher than those of control LPCa and MetPCa (P =.01 and P <.001, respectively). Conclusion: We found higher RAGE expression levels in malignant prostate neoplasia than in BPH. As expected, patients with diabetes had higher scores than control patients. Disease progression and survival parameters were worse in patients with high RAGE levels. RAGE expression may be a useful biomarker for the diagnosis and prognosis of prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: Basal cell carcinoma is the most common malignancy in in the Caucasian race and is a serious health problem with its ever-increasing incidence and high cost. Although the treatment is surgical, some elderly patients do not accept surgical intervention. In this case, non-surgical treatments come into prominence. The Hypericum perforatum (HP) / St. John's Wort plant has been used in the treatment of many diseases for centuries among local people. Here, we aimed to aimed to elucidate the effect and molecular mechanism of the HP plant on BCC cells. Methods: Human BCC cell lines TE 354.T were acquired from ATCC®, then were cultured in Dulbecco's Modified Eagle's Medium. BCC cells were seeded at a concentration of 2x106cells in each flask (n=12). After incubation, while six of the flasks were applied with a 0.8% HP extract and 99.2% medium for 48 hours, no application was made to the control group. The effects of HP on mitochondrial mediated intrinsic and extrinsic apoptotic pathway agents, cell cycle G2 / M checkpoint kinases and inflammatory mediators were investigated in BCC cancer cells. The expression and activities of these mediators in both groups were evaluated by ELISA test. Results: It was determined that HP extract treatment increased the expression of apoptotic proteins (AIF, GADD153, GRP78, caspase-3, Bax) and cell cycle G2 / M checkpoint kinase (Wee1), though it reduced antiapoptotic protein (Bcl-2) and inflammatory mediators (iNOS, COX-2, cPLA2, NFkB) in BCC cell lines. Conclusion: HP extract can support routine chemotherapy on BCC cells with its apoptotic, anti-inflammatory and anti-cancer effect, and may be a beacon of hope in reducing resistance to chemotherapeutic drugs in the treatment of BCC. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) have anti‐inflammatory effects. One specific PUFA, alpha‐linolenic acid (ALA), shows both anti‐inflammatory and antioxidant properties. In the testes, inflammatory mediators are known to increase when orchitis is induced by bacterial lipopolysaccharide (LPS). This study aimed to determine whether the anti‐inflammatory properties of ALA could have a protective effect against LPS‐induced orchitis in mice. The mice were divided into untreated control, orchitis and ALA‐treated orchitis groups. Orchitis was induced by intraperitoneal injection of LPS. The ALA‐treated group was administered ALA by gavage three days before intraperitoneal LPS injection. Cyclooxygenase‐2 (COX‐2), cytosolic phospholipase A2 (cPLA2), inducible nitric oxide synthase (iNOS) enzymes and nuclear factor kappa‐B (NF‐κB) in the testes, as well as serum interleukin 6 (IL‐6) and tumour necrosis factor‐alpha (TNF‐α), were analysed using enzyme‐linked immunosorbent assay (ELISA) tests. LPS administration increased the expression of several inflammatory mediators, including IL‐6, TNF‐α and NF‐κB, as well as the COX‐2, cPLA2 and iNOS enzymes. ALA administration significantly prevented the LPS‐induced increases in these inflammatory mediators and enzymes (p <.05). The anti‐inflammatory and antioxidant effects of ALA may make it a useful candidate for the treatment of orchitis caused by bacterial LPS. [ABSTRACT FROM AUTHOR]

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Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i.p; intraperitoneally) and 200 mg/kg alpha-linolenic acid (gavage) are administered to mice for 9 days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the possible roles of phospholipase C, protein kinase C, and endothelin-converting enzyme on contractions induced by ethanol (164 mM) in isolated gastric fundal strips of mice. Materials and methods: After the mice were killed, the stomach of each was removed and longitudinal muscle strips were prepared from the gastric fundus. The strips were mounted in organ baths and their responses were recorded isometrically. Ethanol (164 mM) was added to the organ baths and a steady-state contraction was obtained. After the first ethanol response was recorded, the preparations were incubated separately with lidocaine (1-100 µM), neomycin (10-500 µM), safingol (0.5-5 µM), and SM-19712 (1-50 µM) for 40 min. The second ethanol response was then examined in the presence of the drug used in the incubation period. Results: Lidocaine (1-100 µM), a local anesthetic agent, did not modulate the contractions induced by ethanol in isolated gastric fundal strips of mice. In contrast, neomycin (10-500 µM), a selective inhibitor of phospholipase C, and safingol (0.5-5 µM), a selective inhibitor of protein kinase C, decreased the ethanol-induced contractions. SM-19712 (1-50 µM), a selective inhibitor of endothelin-converting enzyme, failed to affect these contractions. Conclusion: The contractile effect of ethanol may be muscular rather than neuronal in the gastric fundal strips of mice. In addition, phospholipase C and protein kinase C pathways may have a role in contractions due to ethanol in the mouse gastric fundus. On the other hand, endothelin-converting enzyme may not have a regulatory role in the contractile responses of ethanol in the same tissue. [ABSTRACT FROM AUTHOR]

Objective: Hypericum perforatum, which have various names locally such as "sarı kantaron, kanotu, kilicotu, mayasilotu, yaraotu", is a plant which blooms between july and september at farms, borders of roads and woods, top of hills and grasslands, whose anti-inflammatory and antioxidant effects are shown in various studies. Due to this reason, we planned a study to examine the protective effects of Hypericum perforatum on ototoxicity caused by gentamicin. Methods: For this purpose, 100 mg/kg gentamicin and 70 mg/kg Hypericum perforatum extract are administered to mice for 9 days. On the 9th and 10th days rotarod performance was assessed to evaluate the Gentamicin and Hypericum Perforatum extract on motor coordination of mice. Results: Gentamicine treatment decreased fall latency of mice and Gentamicine together Hypericum Perforatum extract treatment increased fall latency of mice. Conclusion: Our study showed that Hypericum Perforatum extract will be usefull to prevent gentamicin induced ototoxicity [ABSTRACT FROM AUTHOR]

Aim To evaluate the inhibitory effects of ornidazole on the proliferation and migration of metastatic melanoma cell line (B16F10) in vitro and its anti-cancer effects in vivo using a melanoma mouse model. Methods We investigated the effects of ornidazole on cell viability (Crystal Violet and MTT assay) and migration ability (wound-healing assay) of B16F10 melanoma cells, and its ability to trigger DNA damage (Comet assay) in vitro. We also sorted CD133+ and CD133- cells from B16F10 melanoma cell line and injected them subcutaneously into Swiss albino mice to induce tumor formation. Tumor-bearing mice were divided into control and treatment groups. Treatment group received intraperitoneal ornidazole injections. Tumors were resected. Real-time polymerase chain reaction was used to determine the expression of genes involved into Sonic hedgehog (Shh) signaling pathway, stemness, apoptosis, endoplasmic reticulum (ER) stress, ER stress-mediated apoptosis, and autophagy. Shh signaling pathway-related proteins and CD133 protein were analyzed by ELISA. Results Ornidazole effectively induced DNA damage in CD133+ melanoma cells and reduced their viability and migration ability in vitro. Moreover, it significantly suppressed tumor growth in melanoma mouse model seemingly by inhibiting the Shh signaling pathway and ER-stress mediated autophagy, as well as by activating multiple apoptosis pathways. Conclusions Our preclinical findings suggest the therapeutic potential of ornidazole in the treatment of metastatic melanoma. However, larger and more comprehensive studies are required to validate our results and to further explore the safety and clinical effectiveness of ornidazole. [ABSTRACT FROM AUTHOR]

Aim: Apoptotic pathways are important for resistance to chemotherapeutics drugs and cancer development. Metformin is a safe, inexpensive and effective drug used to treat type 2 diabetes. Furthermore, although there is evidence of anticancer effects, the mechanisms by which metformin exerts the effects are unclear. Therefore, it was aimed to investigate Bcl-2, kaspaz-3, bax, wee-1, AIF, grp78 and gadd153 levels in metformin treated skin cancer cells. Materials and Methods: The skin cancer cells (B16F10) were treated with metformin and kaspase-3, bcl-2, wee 1, gadd153, grp78 and AIF levels were analyzed by using ELISA. Result: Treatment of metformin increased of proapoptotic proteins (kaspase-3, bcl-2, wee 1, gadd153, grp78 and AIF) and decreased antiapoptotic protein (bcl-2). Conclusion: In conclusion, this study showed that metformin has apoptotic effect on melanoma skin cancer. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the inhibitory effects of ornidazole on the proliferation and migration of metastatic melanoma cell line (B16F10) in vitro and its anti-cancer effects in vivo using a melanoma mouse model., Methods: We investigated the effects of ornidazole on cell viability (Crystal Violet and MTT assay) and migration ability (wound-healing assay) of B16F10 melanoma cells, and its ability to trigger DNA damage (Comet assay) in vitro. We also sorted CD133+ and CD133- cells from B16F10 melanoma cell line and injected them subcutaneously into Swiss albino mice to induce tumor formation. Tumor-bearing mice were divided into control and treatment groups. Treatment group received intraperitoneal ornidazole injections. Tumors were resected. Real-time polymerase chain reaction was used to determine the expression of genes involved into Sonic hedgehog (Shh) signaling pathway, stemness, apoptosis, endoplasmic reticulum (ER) stress, ER stress-mediated apoptosis, and autophagy. Shh signaling pathway-related proteins and CD133 protein were analyzed by ELISA., Results: Ornidazole effectively induced DNA damage in CD133+ melanoma cells and reduced their viability and migration ability in vitro. Moreover, it significantly suppressed tumor growth in melanoma mouse model seemingly by inhibiting the Shh signaling pathway and ER-stress mediated autophagy, as well as by activating multiple apoptosis pathways., Conclusions: Our preclinical findings suggest the therapeutic potential of ornidazole in the treatment of metastatic melanoma. However, larger and more comprehensive studies are required to validate our results and to further explore the safety and clinical effectiveness of ornidazole.