Comparison between the role of n-acetylcysteine alone and with silymarin in paracetamol induced acute hepatotoxicity [clinical and experimental study]

Paracetamol [APAP], a widely used analgesic and antipyretic, is known to cause hepatic injury in high doses. N-acetylcysteine [NAC] and silymarin have been used in treatment of liver diseases of varying origins. This work was conducted to compare between the role of NAC alone and with silymarin in paracetamol induced acute hepatotoxicity. This work included both clinical and experimental studies. The clinical study included 27 patients with acute paracetamol poisoning admitted to Poisoning Treatment Unit - Zagazig University Hospitals between January and July, 2011. Sixteen patients [group I] were treated with NAC alone. Another eleven patients [group II] were treated with both NAC and silymarin. Plasma paracetamol level was measured on admission and liver function tests were assessed on admission and daily for three days. The experimental study included forty two adult male albino rats were divided into 7 groups. Group [1]: negative control rats, group [2]: positive control rats received distilled water, group [3]: received 140mg/kg NAC, group [4]: received 40mg/kg silymarin, group [5]: received l000mg/kg APAP, group [6]: received APAP followed by NAC in the same previous doses/ Group [7]: received combined NAC and silymarin following APAP administration in the same previous doses. All drugs were given once by oral gavage. 24 hours after commencing the experiment liver function tests and hepatic glutathione [GSH] content were assessed. Liver specimens were submitted to histopathological examination and immunolocalization of BCL-2 and BrdU. It was found that combined treatment with NAC and silymarin induced a significant reduction of the elevated hepatic transaminases compared to treatment with NAC alone in both patients and rats especially patients presented late after 15 hours of APAP ingestion. Histopathological examination of hepatic specimens from combined treated rats revealed reappearance of the regular morphology of the hepatic lobules with strong immunoreactivity to BCL-2 and BrdU. Rats treated with NAC alone showed partial improvement where there were some areas of hepatocytes vacuolization, cellular infiltration, and sinusoidal dilatation, with moderate reaction for both BCL-2 and BrdU. This was accompanied with a significant elevation of the mean values of hepatic GSH in combined treated rats compared to those treated with NAC alone. It was concluded that both silymarin and NAC have a synergistic effect, and combined treatment with both of them could be used as a beneficial treatment for paracetamol acute hepatotoxicity especially for late presented cases

Effect of bisphenol A on the myocardium of adult male albino rats and the possible role of lycopene: a histological and biochemical study

Despite the wide use of bisphenol A [BPA] in plastic and epoxy resin industries, its side effects have been a subject of controversy. Lycopene [a natural carotenoid] has a protective role in many cardiovascular diseases. This work aimed to study the biochemical and structural changes induced by BPA in the myocardium of adult rats and evaluate whether coadministration of lycopene could alter these effects. Twenty adult male albino rats were divided into four equal groups. Group I was the control. Group II received lycopene [4mg/kg body weight/day orally] for 8 weeks. Group III was given BPA [50mg/kg body weight/day orally] for 8 weeks. Group IV was given both BPA and lycopene in the same previous dose and for the same duration. At the end of the experiment, rats were anesthetized, and their hearts were taken and prepared for histological and biochemical studies. Area percentages of the collagen content and positive immune reaction for vimentin were morphometrically and statistically analyzed. Examination of group III revealed that some myocytes had a deeply acidophilic cytoplasm and were devoid of nuclei. Some myocytes appeared with pale vacuolated cytoplasm, and some had focal loss of myofibrils. Their sarcoplasm contained many distorted mitochondria and dilated T-tubules. Their nuclei were variable in shape. They were peripherally located, or deeply indented, or heterochromatic. Many interstitial cells, inflammatory cells, congested blood capillaries, and areas of edema were seen. A significant increase in collagen fibers and in the area percentage of positive immune reaction for vimentin compared with the control group was observed. Examination of group IV showed that the cardiac muscle cells had a normal architecture except for a few distorted muscle fibers and many congested blood capillaries. There was a significant decrease in the area percentage of positive immune reaction for vimentin in group IV compared with group III. The current study revealed significant increase in serum malondialdehyde, whereas tissue reduced glutathione and catalase showed significant decrease in group III compared with the control group. In contrast, in group IV, malondialdehyde showed significant decrease, and tissue reduced glutathione and catalase showed significant increase, compared with group III. Long-term exposure to BPA could induce structural and biochemical changes in rat cardiac muscle. This could be partially minimized by concomitant administration of lycopene

Evaluation of the possible protective effect of aloe vera against reproductive toxicity induced by diazinon in adult albino rats

Diazinon, an organophosphate insecticide has been used in agriculture and domestic for several years. This work was undertaken to investigate the toxic effects of diazinon on reproductive systems in adult albino rats of both sexes and to assess the protective effects of aloe vera against these toxic effects. A total of 60 adult albino rats of both sexes were equally divided into five groups. Twelve rats served as the negative control [group 1], another twelve rats were used as positive control group [group 2] received deionized water [the vehicle]. The remaining thirty-six rats were equally divided into three groups. Rats in group 3 were treated with aloe vera in a dose of 300 mg/kg, while those of group 4 received 12.8 mg/kg of diazinon. Rats in the 5[th] group were treated with aloe vera followed by diazinon. For each group, it was further subdivided into two subgroups; a-subgroup for male rats and bsub group for female rats. Chemicals and vehicle were administered by gavage on a daily base for eight weeks. By the end of the study, all rats were sacrificed for collection of blood samples for evaluation of testosterone, estradiol and progesterone. Testicular and ovarian specimens were collected for assessment of oxidative stress markers and histopathological examination. Diazinon significantly reduced the serum levels of testosterone in male rats and estradiol and progesterone in female rats. Diazinon induced disorganized degenerated germinal epithelium with edema between the seminiferous tubules and degeneration of the corpora lutea and ovarian follicles. These changes were accompanied with increased caspase-3 immunoreactivity and significant decreases in testicular and ovarian glutathione [GSH] levels, activity of superoxide dismutase [SOD] enzyme and a significant increase in malonaldehyde levels. Also it was observed that aloe vera treatment diminished diazinon induced detrimental effects in both testis and ovary. Diazinon induced testicular and ovarian damage might be due to oxidative stress and free oxygen radicals production upon diazinon exposure, inducing histopathological alterations and promoting local apoptosis via activation of caspase-3 pathway; however, aloe vera seems to be an effective antioxidant against diazinon induced testicular and ovarian toxicity