Zeynep Aksungur

Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats

The objective of the present study is the treatment of oxidative damage caused by acrylamide induced oxidative stress in rats with the administration of a strong antioxidant, namely crocin. High acrylamide (AA) levels have genotoxic, carcinogenic and neurotoxic effects on living organisms. In the present study, 40 Wistar rats were randomly divided into four equal groups. These groups were control, acrylamide (25mg/kg), crocin (50mg/kg), acrylamide+crocin (25mg/kg acrylamide and 50mg/kg crocin) groups. At the end of the application, biochemical and histological variations were examined in liver and blood samples. It was observed that acrylamide administration significantly decreased liver GSH and TAS levels when compared to the control group. On the contrary, it was also observed that AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels increased as a result of acrylamide administration. Histopathological examinations demonstrated inflammatory cell infiltration, hepatocellular necrosis and hemorrhage areas in AA group liver sections. Furthermore, intracytoplasmic vacuolization was detected in hepatocytes. After crocin treatment, it was observed that GSH and TAS levels increased while AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels decreased. Significant decreases were observed in inflammatory cell infiltration and vascular congestion in liver sections and intracytoplasmic vacuolization in hepatocytes after the crocin treatment, while no hepatocellular necrosis and hemorrhages were observed. In the present study, it was demonstrated that crocin treatment removed acrylamide induced liver damage due to the strong antioxidant properties of crocin.

Biochemical investigation of the toxic effects of acrylamide administration during pregnancy on the liver of mother and fetus and the protective role of vitamin E

Abstract Objectives: To investigate the toxic effects occurring in the liver tissues of the pregnant rats and the fetuses, which are administered acrylamide and vitamin E as a protector during pregnancy. Materials and methods: This research was conducted with the permission of Laboratory Animals Ethical Board of Inonu University Faculty of Medicine. Forty rats, of which their pregnancy is validated via vaginal smear, were distributed into five different groups. On the 20th day of pregnancy, pregnant rats and fetuses are decapitated. Malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS) and xanthine oxidase (XO) levels were measured in the liver samples taken from mother and fetuses. Results: It was detected that acrylamide administered during pregnancy increased MDA, TOS, XO levels statistically significantly and decreased the GSH level (p ≤ 0.05) in the pregnant rat liver tissue when compared to all other groups. In the vitamin E administered group; GSH, TAS levels significantly increased statistically and TOS and XO levels dropped to levels of the control group (p ≤ 0.05), in comparison to all other groups. Among all groups, no biochemical changes were observed in the fetus liver tissue (p > 0.05). Conclusion: The liver of pregnant rats functions as a protective pre-filter by detoxifying acrylamide effectively and the acrylamide that reaches fetus liver is detoxified by the cytochrome P-450 system of the fetus liver. To be able to figure out the biochemical mechanism, more advanced studies are needed.

Effects of molsidomine on retinal ischemia/reperfusion injury in rabbits

Abstract We investigated the effect of molsidomine (MOL) on ischemia/reperfusion (I/R) injury. Rabbits were assigned to four groups: group 1, sham; group 2, I/R; group 3, MOL treatment for 4 days after I/R; group 4, MOL treatment for 1 day before I/R and 3 days after I/R. Retinal I/R was produced by elevating the intraocular pressure to 150 mm Hg for 60 min. Seven days after I/R, the eyes were enucleated. Retinal changes were examined using histochemistry. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) also were measured. We found a significant increase in the thickness of the outer nuclear layer of group 3 compared to the other groups. In groups 3 and 4, caspase-3 stained cells in the ganglion cell layer were decreased compared to group 2. We found a significant increase in caspase-3 stained cells in the inner nuclear layer (INL) of group 2 compared to the other groups. We found a significant increase in caspase-3 stained cells in group 3 compared to group 4 in the INL. The MDA level in group 2 was significantly higher than group 1 and MOL significantly decreased MDA levels in groups 3 and 4. We found that MOL protected the retina from I/R injury by enhancing antioxidative effects and inhibiting apoptosis of retinal cells.

Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome

Background. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS.

The effects of acrylamide and vitamin E on kidneys in pregnancy: an experimental study

Abstract Objectives: The objective of this study is to investigate possible damages to kidney tissues of pregnant rats and their fetuses exposed to acrylamide during pregnancy and possible protective effects of vitamin E against these damages. Material and methods: Rats were randomly assigned to five groups of control, corn oil, vitamin E, acrylamide, vitamin E + acrylamide, six pregnant rats in each. Mother and fetal kidney tissues were examined for malondialdehyde (MDA), reductase glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), total oxidant status (TOS), urea, creatine, trace elements such as Zn and Cu in the serum and histopathological analyses were conducted. Results: It was determined that acrylamide, administered during pregnancy, statistically significantly increased MDA and TOS levels, maternal serum urea, creatinine, and Zn levels, while it decreased GSH, TAS, SOD, and CAT levels (p ≤ .05) when compared with all other groups in the kidney tissues of pregnant rats and their fetuses and caused tubular degeneration, hemorrhage, narrowing, and closure in Bowman’s space, and, in the E vitamin group, it statistically significantly increased GSH, TAS, SOD, CAT, urea, creatinine, and Zn levels when compared with other groups and lowered TOS and MDA levels to those of the control group (p < .05) and there were no differences between the groups histologically. Conclusion: It was observed that acrylamide administered during pregnancy caused oxidative stress in kidney tissues of mother rats and their fetuses, resulting in tissue damage, and vitamin E application, which is considered to be a powerful antioxidant, inhibited oxidative stress.

Biochemical changes induced by grape seed extract and low level laser therapy administration during intraoral wound healing in rat liver: an experimental and in silico study

In the present study, the changes that occur in rat liver tissue as a result of the use of grape seed extract (GSE) and low level laser therapy (LLLT) in intraoral wound (IW) healing are analyzed using biochemical parameters. Diode laser application groups received 8 J/cm2 dose LLLT once a day for 4 days (810 nm wavelength, continuous mode, 0.25 W, 9 s). As a result of the biological parameter analysis, it was determined that the oxidative damage caused by the IWs and recovery period on 7th and 14th days could be substantially removed with GSE applications that have antioxidant capacity especially in rat liver tissue. In addition, the active compound of grape seed, catechin is studied in the active site of glycogen synthase kinase 3 (GSK3) target using molecular modeling approaches. Post-processing molecular dynamics (MD) results for catechin is compared with a standard GSK3 inhibitor. MD simulations assisted for better understanding of inhibition mechanism and the crucial amino acids contributing in the ligand binding. These results along with a through free energy analysis of ligands using sophisticated simulations methods are quite striking and it suggests a greater future role for simulation in deciphering complex patterns of molecular mechanism in combination with methods for understanding drug-receptor interactions.

Protective effect of dexpanthenol against cisplatin‑induced hepatotoxicity

The aim of the present study was to investigate the protective effect of dexpanthenol (Dexp) against cisplatin (Cis)-induced hepatotoxicity. Thirty-two Sprague Dawley rats were divided into four groups: Control group (n=8), Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp), Cis group (n=8, 7 mg/kg/ip/single dose Cis) and Cis+Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp +7 mg/kg/ip/single dose Cis). MDA, CAT, GSH, GSH-Px, TOS, TAS, OSI, Total Nitrit, IL-1β, IL-6 and TNF-α levels were analyzed in liver tissue samples. After paraffinization of liver tissue samples, histopathological (congestion, loss of glycogen, number of Kupffer cells) and immunohistochemical (caspase-3 expression) parameters were assessed on the paraffinized liver sections. GSH, TAS, TOS, OSI, Tot Nit, L-Arginine, ADMA and SDMA levels were measured in the serum samples. Statistically significant differences were found between the groups in terms of all liver tissue biochemical parameters, with the exception of IL-1β and TNF-α levels. GSH, CAT, GSH-Px, TAS and Tot Nit levels were significantly higher in the Cis+Dexp group compared to the Cis group, whereas MDA, TOS, OSI and IL-6 levels were higher in the Cis group. Similarly, serum GSH, TAS, Tot Nit levels were higher in the Cis+Dexp group whereas TOS, L-Arginine, ADMA and SDMA levels were higher in Cis group. There were statistically significant differences between Control and Cis groups in terms of congestion increase, increase of glycogen loss, increase of Kupffer cell number and increase of caspase-3 expression (P<0.001). There was a statistically significant difference between the Cis and the Cis+Dexp groups in terms of histopathologic parameters, with the exception of congestion (P<0.001). To conclude, histopathological, immunohistochemical, and biochemical results of this study demonstrated that Dexp has a protective effect against Cis-induced hepatotoxicity.

Investigation of the protective effects of crocin on acrylamide induced small and large intestine damage in rats

Abstract We investigated repair of acrylamide (AA) induced damage in intestines by administration of crocin. We used 40 male Wistar rats in four groups of 10 animals: control, AA, crocin, and AA + crocin groups. We investigated biochemical and histological changes to small and large intestine. AA ingestion decreased glutathione (GSH) levels and total antioxidant status (TAS) in the intestine compared to the control group, while superoxide dismutase (SOD) and catalase (CAT) activities, and total oxidant status (TOS) and malondialdehyde (MDA) levels were increased. Villi were shortened and villus degeneration was observed in ileum of the AA group. Degeneration of surface epithelium and Liberkühn crypts were observed in colon sections. GSH and TAS levels increased after administration of AA together with crocin, while SOD and CAT levels and TOS and MDA levels decreased; significant recovery of histological damage also was observed. We found that crocin exhibits protective effects on AA induced small and large intestine damage by inhibiting oxidative stress.

Thymoquinone is protective against 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity

Abstract We investigated changes in rat liver tissues following administration of thymoquinone (TQ) against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced hepatotoxicity. Fifty rats were assigned randomly to five groups of 10 as follows: control, corn oil, TCDD, TQ and TCDD + TQ. Biochemical and histopathological analyses were conducted on liver tissue. We found that 30 day TCDD administration caused histopathological changes in liver including thickening of Glisson’s capsule, intracytoplasmic vacuolization in hepatocytes, sinusoidal dilation, vascular and sinusoidal congestion and inflammatory cell infiltration. TCDD administration increased malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels in rat liver tissue and reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) levels compared to all other groups. In the TQ treated group, GSH, SOD, CAT and TAS levels increased compared to all other groups. MDA, TOS, ALT, AST, ALP levels decreased compared to all other groups. Our histological findings were consistent with the biochemical findings. The oxidative and histologic effects of TCDD were eliminated by TQ treatment. TCDD administration caused oxidative stress in rat liver and TQ administered with TCDD prevented TCDD induced hepatotoxicity. TQ could be considered an alternative anti-TCDD toxicity agent.

Neuroprotection against CCl4 induced brain damage with crocin in Wistar rats

ABSTRACT Owing to its lipophilic property, carbon tetrachloride (CCl4) is rapidly absorbed by both the liver and brain. We investigated the protective effects of crocin against brain damage caused by CCl4. Fifty rats were divided into five groups of ten: control, corn oil, crocin, CCl4 and CCl4 + crocin. CCl4 administration decreased glutathione (GSH) and total antioxidant status (TAS) levels, and catalase (CAT) activity, while significant increases were observed in malondialdehyde (MDA) and total oxidant status (TOS) levels and superoxide dismutase (SOD) activity. The cerebral cortex nuclear lamina developed a spongy appearance, neuronal degeneration was observed in the hippocampus, and heterochromatic and pyknotic neurons with increased cytoplasmic eosinophilia were observed in the hippocampus after CCl4 treatment. Because crocin exhibits strong antioxidant properties, crocin treatment increased GSH and TAS levels and CAT activities, and decreased MDA and TOS levels and SOD activity; significant improvements also were observed in histologic architecture. We found that crocin administration nearly eliminated CCl4 induced brain damage by preventing oxidative stress.