The Modulatory Effects of Pentoxifylline in Biochemical Changes Induced By 17α-Ethinyl Estradiol in the Rat Model

Background: Ethinylestradiol (EE) has induced cholestasis and hepatotoxicity in animal studies through reducing bile acid uptake by hepatocytes and induce of oxidative stress. Pentoxifylline (PTX) is a drug that by inhibition of release or transcription of proinflammatory cytokine cause prevents oxidative stress of liver cell and reduction of damage. We aimed to evaluate the effects of pentoxifylline on liver injury induced by Ethinylestradiol in rats. Methods: Twenty-four female Wistar rats (300±20 gr) were divided into four groups, equally. Duration of treatment was 5 consecutive days for each group. The control group Simultaneously received orally and subcutaneously normal saline. PTX group Simultaneously received Pentoxifylline orally and normal saline subcutaneously, EE Group Simultaneously received EE subcutaneously and normal saline orally. In the EE+PTX group, rats Simultaneously received EE subcutaneously and PTX orally. Rats were anesthetized and blood and tissue samples were collected for measurement of hematological and biochemical parameters. Results: The EE administration increased the serum levels of ALP and MDA significantly. The EE administration also decreased albumin and GPX levels were significant. These aberrations were improved by PTX treatment in EE + PTX group. Most of hematological parameters were not significant by the EE. The plasma level of TNF- in the PTX+ES treated group showed a significant decrease in comparison to that in the ethinyl estradiol group. Conclusion: PTX has partial capacity to protect against liver changes induced by Ethinyl Estradiol

The Role of TNF-α in Aflatoxin B-1 Induced Hepatic Toxicity in Isolated Perfused Rat Liver Model

Aflatoxin B-1 (AFB1) is one of the major mycotoxins causing food contamination. Previous studies have shown that AFB1 can induce carcinogenicity and toxic effects in the isolated perfused rat liver and these effects are associated with its metabolites and peroxidation activity. Here we surveyed whether these pathogenic effects of AFB1 are associated with TNF-α as an inflammatory cytokine in general liver damages. In this study, we used twenty male Wistar rats (250-300 g). Rats were divided into four groups. Control group was pre-treated with LPS and then perfused with KHBB. The second group was pretreated with PTX and LPS and then perfused with KHB. The third group was pre-treated with LPS and then perfused with AFB-1 and KHB. The last group was pretreated with LPS and PTX and then perfused with AFB1 and KHB. Results revealed that aflatoxin B1 significantly increased the enzyme activity of aminotransferase and levels of lipid peroxidation. Also, the levels of Glutathione decreased in the aflatoxin group significantly. TNF-α released in perfusate and increased in aflatoxin B1 group significantly and decreased in AFB-1+PTX. Exposure to Aflatoxin B1 may induce reactive oxygen species, so these species may induce overproduction of proinflammatory cytokines such as TNF-α and may cause more damage to hepatic cells

Co-Exposure Effects of LPS with Various Aflatoxin B1 Doses in Isolated Perfused Rat Liver Model

Background: Activation of inflammatory cells can cause more chemicals induced-hepatotoxicity. Aflatoxin B1 (AFB1) is a fungal toxin that induces acute hepatotoxicity in humans and animals. This study was conducted to examine the effect of co-exposure LPS and various aflatoxin B1 doses on the damage hepatic parameters in isolated perfused rat liver. Methods: Thirty-two male wistar rats (250-300g) were divided to eight groups including Control and LPS; three groups with various doses of AFB1 (0.01, 0.1 and 1 ppm) and three groups with various doses of AFB1 and Lipopolysaccharide (LPS) (300 ppm). Activity of Aspartate transaminase (AST) and Alanine transaminase (ALT) were determined in perfusate. Thiobarbituric acid reactive substances (TBARS) and Glutathione (GSH) concentrations were measured in homogenate liver. Results: At two groups of AFB 1 (with LPS and without LPS) at AFB1 concentrations of 0.1 and 1 ppm, elevation of AST and ALT enzymes activity were indicated. Values of GSH in both of groups (AFB 1 with LPS and without LPS) had reduced at concentration of 1 ppm. TBARS concentrations were enhanced in AFB1 concentration of 1 ppm in both of groups (with LPS and without LPS), however in comparison between groups (with LPS and without LPS) in similar concentrations significant different did not observe (P<0.05). Conclusion: Non-injurious dose of LPS did not enhance liver susceptibility to various doses of AFB1 in perfused rat liver. This may be in part of due to extrahepatic factors, which contribute, in more liver damage

Evaluation of aglepristone and oxytocin on induction of parturition in guinea pig

Induction of parturition in guinea pigs appears to be essential because these animals have a higher rate of reproductive problems than rabbits and small rodents. Since aglepristone (AGL) is a competitive progesterone antagonist acting through binding to progesterone receptors while oxytocin (OT) is a powerful constituent of uterine smooth muscle, the aim of this study was to evaluate the clinical and ultrasonographic impacts of AGL and OT on guinea pig parturition induction. In this study, guinea pigs were allocated into five groups; each included five animals on the 61st day of pregnancy. In the aglepristone group (Agle), AGL was administrated subcutaneously (SC) once daily on 2 consecutive days (Days 61 and 62 post mating). Oxytocin (OT) was administered subcutaneously once and twice at 4-h intervals on Day 62 post mating in oxytocin 1 (Oxy1) and oxytocin 2 (Oxy2) groups, respectively. The animals in the aglepristone-oxytocin group (Agle-Oxy) received AGL subcutaneously once daily on 2 consecutive days (Days 61 and 62 post mating) and OT on Day 62 post mating. The remaining sows received saline solution (0.9% NaCl) in the control group. According to the results, fetal heart rate, temperature, neonatal and maternal survival rates were not significantly different between the treatment and control groups (p > 0.05). Biparietal diameter of head and body weight of neonates in the Agle, Oxy2 and Agle-Oxy groups showed a significant decline, compared to the control group (p < 0.05). The time interval between injection and delivery and the duration of pregnancy was significantly reduced in Agle, Oxy2, Agl-Oxy groups, compared to the control and Oxy1 groups. In conclusion, it seems that treatment Oxy2 can induce parturition in guinea pigs without side effects and lower pain during induction of parturition