Study of the effect of pentoxifylline in hepatlc ischemia-reperfusion injury in albino rats

Hepatic ischemia reperfusion injury [IRI] is a common pathological process of traumatic surgical diseases in the liver, liver transplantation, shock and infection. Inflammatory mediators are implicated in the pathogenesis of IRI. Pentoxifylline [PTX] is a derivative of methylxanthine, acts as a phosphodiesterase inhibitor and therapy elevares the levels of cAMP. Interest in PTX has been recently reawakened because of its reported suppressive action on immune functions, particularly on cytokine production. It has been shown to be beneficial in organ transplantation. Pentoxifyllin probably acts primarily by inhibiting tumor necrosis factor-alpha [TNF-alpha]. We hypothesized that PTX treatment would attenuate hypoxic ischemic liver injury. Thirty-six male albino rats were used throughout this experiment. Animals were divided into 2 main groups; each comprised 18 rats [sham-operated and IRI groups]. Group [1] sham-operated [exposed to anesthesia and laparotomy], this group is subdivided into 3 equal subgroups. Subgroup 1A: Sham-operated received daily intra-gastric saline, subgroup IB: sham-operated +PTX [8mg/kg/day] for 6 successive weeks before exposure to anesthesia and laparotomy, subgroup IC: as IB but received PTX [16mg/kg/day]. Group [II]: IRI group, divided into 3 equal subgroups, sub- group llA received intra-gastric saline for 6 weeks before the induction of IRI ,subgroup 116, received 8mg/kg/day PTX intra-gastrically for 6 weeks before induction of IRI, subgroup IIB, recieved 8mg/kg/day PTX intra-gastrically for 6 weeks before induction of IRI, subgroup IIC, received PTX [16 mg/kg/day] before induction of IRI. It was found that IRI produced significant increase in plasma alanine transaminase [ALT], malondialdehyde [MDA], TNF-alpha and hepatic tissue calcium content as compared to sham-operated animal groups. Intra- gastric administration of PTX in the small or large doses for 6 weeks before induction of IRI produced no significant change in the hepatic tissue calcium, plasma MDA, ALT and plasma TNF-alpha as compared to sham control group, but it produced significant decrease as compared to IRI control group. On the light of the present study, these preliminary results with PTX are encouraging to recommend further human studies in hepatic patients especially whom are given PTX for associated cardiovascular problems

Evaluation of the anti-ischaemic effect of selective COX-2 inhibitor [rofecoxib] in permanent left middle cerebral artery occlusion [focal cerebral ischemia model] in rats

Cyclooxygenase-2 [COX-2] enzyme is induced in the central nervous system after various insults. It has been localized to neurons and in cells associated with the cerebral vasculature where the system is involved in the inflammatory component of the ischaemic cascade. COX-2 is part of the initial reaction that involves the arachidonic acid cascade, which produces molecules that involved in inflammatory response. The present of study evaluated the pharmacological effects of a specific COX-2 inhibitor [rofecoxib], in a permanent focal cerebral ischaemia model in albino rats and its effects were compared to those of calcium channel blocker [nimodipine]. Experiments were carried out on sixty male albino rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion. Rofecoxib and nimodipine were administered 30 minutes after the occlusion of middle cerebral artery [MCA] and then daily IP for successive 6 days during which neurobehavioral evaluation was done. On the 7[th] day of occlusion, the infarction size, was measure and the remote hippocampal cell death were determined. Treatment with either rofecoxib or nimodipine caused significant equal improvement of the neurological score, significant attenuation of the infarction size and hippocampal cell death. While, the decrease of the infarction size was 50% by both drugs, the percentage of reduction of hippocampal degeneration was only 10% by both drugs. This difference in the percentage of improvement of infarction sizes and hippocampal degeneration may be due to presence of the hippocampus in a remote site from MCA blood supply. The present study suggests that COX-2 plays an important role in the ischaemic cascade of events. Furthermore, selective COX-2 inhibitors may be useful in the treatment of ischaemic stroke to improve motor functions

Effect of pentoxifylline on adjuvant-induced arthritis in albino rats

Rheumatoid arthritis [RA] is a common inflammatory autoimmune disorder. Non-steroidal anti inflammatory drugs [NSAIDs] have become an integral part of RA therapy. Adverse effects of these drugs are widely expanding. Data implicate the cytokine tumor necrosis factor alpha [TNF-alpha] in the pathophysiology of RA as well as involved in the indomethacin induced gastrointestinal damage. Pentoxifylline [PTX], amethylxanthine derivative is documented to possess anti-inflammatory and anti-TNF-alpha properties. The present study was conducted to investigate the effect of PTX on edema, serum malondialdehyde [MDA] and TNF-alpha in experimentally induced collagen II adjuvant arthritis in albino-rats. Forty-two male albino rats weighing 200-250 grams were used throughout the study. The anti mals were divided into seven equal groups. Group [1]: Non-arthritic control rats received daily 0.5 ml intragastric isotonic saline for 6 weeks. Group [2]: Arthritic control rats received daily 0.5ml isotonic saline intragastricaliy for 6 weeks. Group [3]: Arthritic rats treated intragastrically with indomethacin [1.3 mg/kg/day] for 6 weeks. Group [4]: Arthritic rats treated with daily intragastric PTX [50 mg/kg] for 6 weeks. Group [5]: Arthritic rats treated with PTX [100 mg/kg/day], intragastrically for 6 weeks. Group [6]: Arthritic rats treated with PTX [50 mg/kg/day] given 30 minutes before administration of indomethacin [1.3 mg/kg/day], intragatrically for 6 weeks. Group [7]: Arthritic rats treated with PTX [100 mg/kg/day] administered 30 minutes before administration of indomethacin as above. It was found that administration of collagen II and complete freund's adjuvant to rats produced a significant arthritic changes as assessed by paw edema thickness, analgesmetric pressure and C-reactive protein, arthritic rats developed a significant increase in serum MDA and TNF-alpha. Daily intragastric administration of either indomethacin, PTX alone or in combination induced a significant decrease in paw edema thickness, CRP, MDA as well as induced increase in analgesmetric pressure tolerance. Administration of PTX [50 mg or 100mg/kg] to arthritic rats produced significant decrease in TNF-alpha. Mean while administration of indomethacin alone to arthritic rats produced significant increase in TNF-alpha. Administration of PTX [50 or 100 mg/kg/day] 30 minutes before indomethacin induced a significant decrease in TNF-alpha as compared to administration of indomethacin alone. These findings suggest that PTX is effective in treatment of collagen-II induced adjuvant arthritis. In addition the present work support the concept that antagonizing TNF-alpha is successful in treating inflammatory disorder as RA. PTX may have to be used as adjuvant therapy in RA

Effect of prepubertal exposure to cigarette smoke on sexual maturation and the reproductive tissues of female rats

The impact of cigarette smoke on fertility of females has been amply documented, but there has been no attention paid to the possible impact of prepubertal exposure to cigarette smoking on female reproductive capacity. Beginning on the day 15 postnatal life, twenty female albino rats were exposed passively to cigarette smoke [0.5 mg/kg body wt. daily for 30 min] in a special container allowing good areation [cigarette smoke-exposed group]. Under similar conditions, twenty female rats were exposed to room air only [Sham-exposed group]. All rats were weighed every two days till the day of puberty; detected by the vaginal membrane rupture. Also, blood samples were collected on the day 35 postnatal life and on the day of puberty for assay of gonadotropins, prolactin and ovarian hormones which are related to sexual maturation as well as ovarian and uterine functions. On the day of puberty, the uteri and ovaries were weighed. Also, the number of ova were counted. In addition, tissue bath experiments were done to assess the effect of pre-pubertal exposure to cigarette smoke on the contractile response of uterine horns of nonpregnant mature female rats to oxytocin or 5 HT [10.90 ng/ml, 10-90 nM respectively]. In rats exposed to cigarette smoke, as compared to shame-exposed rats, it was found: [1] a significant delayed puberty associated with a significant growth retardation, [2] a significant hyperprolactinemia associated with a significant decline in gonadotropins and ovarian hormones at prepubertal and at the day of ovulation, and [3] a significant increase in the strength of spontaneous uterine contractions, prolonged the duration of their cycles and declined their frequency. The stimulatory effects of both spasmogens [oxytocin or SHT] were potentiated and prolonged. It is suggested that: [1] the neurotransmitter systems may be involved in the mechanisms of the sexual maturation, and [2] The mechanism attributed to cigarette smoked - changes in uterine contractility could be due to phosphatidyl inositol signaling

Hepatoprotective effect of vitamin C and E on experimentally induced hepatotoxicity by carbon tetrachloride in rats

The cytoprotective effects of currently used antioxidants; vitamin E and vitamin C against various types of hepatotoxicity have been reported in previous studies. A model of carbon tetrachloride induced hepatotoxicity was used in current study, to investigate the possible synergistic hepatoprotective role of vitamin E and or vitamin C. The result of the present study showed that administration of either vitamin E [50 mg/kg/day] or vitamin C [2 gram/kg/day] resulted in markedly protective effect against carbon tetrachloride hepatoxicity as indicated by reduced ALT, AST, MDA level as well as improved histological picture. It is concluded that combined administration of vitamin E and C has potentials synergistic hepatoprotective effect against CCL[4] induced hepatotoxicity as vitamin C has a spare action for vitamin E

Effect of vitamin - E on methotrexate hepatotoxicity in rats

The aim of this study was to elucidate the possible role of free radicals in methotrexate [MTX] hepatotoxicity and the protective effect of antioxidant [vitamin E] against MTX hepatotoxicity. Experimental MTX hepatotoxicity was induced by a daily oral administration of 15 mg/kg MTX for four days to Sprague-Dawley rats. The oral co-administration of vitamin E 450 mg/kg with MTX for the same period produced a significant improvement in both the functional parameters and the histopathological picture in the liver of the treated rats. Also, the concomitant administration produced a significant decrease in serum malondialdehyde [MDA] which was significantly increased by MTX alone

Effect of sulphasalazine and meloxicam on adjuvant - induced arthritis, clues to their action

This work was conducted to determine the possible in vivo effect of sulfasalazine and meloxicam on free oxygen radicals in adjuvant- induced arthritis in rats. Twenty-four male albino rats were used and divided into four equal groups. The first group consisted of non- arthritic rats [normal control] received normal saline orally for 21 days. The second group received intragastric saline for the same duration [arthritic control]. Third group consisted of arthritic rats treated with meloxicam in a dose of 0.12 mg/kg/d. The fourth group received sulfasalazine in a dose of 270 mg/kg/d orally for 21 days. The results suggested that sulfasalazine was as effective as meloxicam in the treatment of collagen II adjuvant-induced arthritis as both drugs exerted a free oxygen radical scavenging activity