Irfan Cinar

Biochemical and histologic study of lethal cisplatin nephrotoxicity prevention by mirtazapine

BACKGROUND Cisplatin is a platinum derivative frequently used in the chemotherapy of different solid tumors. This biochemical and histologic study investigated a possible protective effect of mirtazapine with regard to cisplatin-induced nephrotoxicity in the rat. METHODS The animals were divided into 4 groups: 15 mg/kg mirtazapine + 10 mg/kg cisplatin, 30 mg/kg mirtazapine + 10 mg/kg cisplatin, only 10 mg/kg cisplatin and negative control (healthy) group. During 14 days, the treatment and treated control group took drugs, while the healthy animals were given distilled water on the same schedule. All animals were sacrificed by high-dose anesthesia at the end of the 14 days of treatment; their kidneys were removed and subjected to histologic and biochemical study. RESULTS In both of the doses we used, mirtazapine decreased the levels of malondialdehyde, creatinine, blood urea nitrogen and myeloperoxidase activity when compared to cisplatin group. On the other hand, it increased total glutathione level in all doses. Slight histopathological findings were determined in mirtazapine groups when compared to cisplatin control group. CONCLUSION In the light of our results and literature knowledge, we can conclude that the protective effect of mirtazapine in cisplatin toxicity originates from its own antioxidant activity.

The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2).

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate

Abstract Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.

The role of urotensin-II and its receptors in sepsis-induced lung injury under diabetic conditions

Abstract This study aimed to investigate the potential role of urotensin‐II receptors in sepsis‐induced lung injury in diabetic mice using urotensin‐II receptor agonists and antagonists. A total of 110 male CD1 mice were used in this study. Diabetes was induced by 200 mg/kg streptozotocin. One month after diabetes induction, the cecal ligation and puncture‐induced polymicrobial sepsis model was applied in the diabetic and non‐diabetic mice. Low and high doses of human urotensin‐II agonist (HU‐II) and antagonist (palosuran) were administered one hour after sepsis induction. HU‐II administration was repeated in two‐hour intervals. Blood and tissue samples were collected at 6 and 12H after sepsis induction for biochemical, molecular, and histopathologic examinations. Regarding to the lungs mRNA expression and immunohistochemistry results of TNF‐Symbol, IL1 Symbol, IL6, and NF‐SymbolB, it was observed that cytokine levels significantly increased in the diabetes group and the sepsis groups compared to the healthy group; this increase was significantly higher in the diabetes‐sepsis groups. Our biochemical (superoxide dismutase, glutathione, and malondialdehyde) and histopathological findings in the lungs also supported these results. All increased parameters were significantly reduced dose‐dependently by the administration of palosuran, an urotensin receptor antagonist. mRNA expression of urotensin‐II and its receptor were examined in the lung tissue. Palosuran administration significantly reduced the urotensin‐II and urotensin‐II receptor levels that increased in the damaged tissue. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. This study has shown that urotensin‐II and urotensin‐II receptors contribute to the aggravation of sepsis‐induced lung injury in diabetic mice; palosuran prevents this damage by antagonizing urotensin‐II receptors.

Urotensin receptors as a new target for CLP induced septic lung injury in mice

Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1β, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1β, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.

Dose-dependent effect of radiation on resorbable blast material titanium implants: an experimental study in rabbits

Abstract Background: Radiotherapy is a commonly used treatment modality in head and neck cancer; however, it also negatively affects healthy structures. Direct damage to oral soft and hard tissue frequently occurs with radiotherapy. In this study, we aimed to evaluate the effect of radiotherapy on bone surrounding titanium dental implants via biomechanical and molecular methods. Materials and methods: Fifty-four implants were inserted in the left tibiae of 18 adult male New Zealand rabbits (3 implants in each rabbit). After 4 weeks of the implant surgery, the left tibiae of 12 rabbits were subjected to a single dose of irradiation (15 Gy or 30 Gy). Four weeks after the irradiation, rabbits were sacrificed and removal torque test was done for the biomechanical evaluation. Bone morphogenetic protein-2 (Bmp-2) and fibroblast growth factor-2 (Fgf-2) expression analyses were performed with Real-time PCR. Statistical analysis was done using SPSS. Results: The control group showed significantly higher removal torque value than the 15 and 30 Gy irradiation groups, and the 15 Gy irradiation group had higher removal torque value than the 30 Gy irradiation group (p < .001). The 15 Gy and 30 Gy irradiation groups had significantly lower Bmp-2 and Fgf-2 mRNA expressions than the control group (p < .001). In addition, the 30 Gy irradiation group had significantly lower Bmp-2 (p < .01) and Fgf-2 mRNA expressions (p < .001) than the 15 Gy group. Conclusion: Radiotherapy with 15 and 30 Gy doses can adversely affect osseointegration of implants by reducing the quality of bone and impairing the bone-to-implant contact. The mechanism of action seems to be related to alterations in Bmp-2 and Fgf-2 mRNA expressions.