Hepatoprotective activity of Dypsis lutescens against D-galactosamine-induced hepatotoxicity in rats and its phytoconstituents

Objective: To isolate and identify the polyphenolic constituents of Dypsis lutescens, and evaluate the hepatoprotective activity of the ethanolic extract of Dypsis lutescens leaves. Methods: Hepatoprotective, antioxidant and anti-inflammatory effects of two doses of Dypsis lutescens ethanolic leaf extract were investigated in five groups of six rats each administered with the ethanolic extract of Dypsis lutescens leaves. Liver function parameters were assessed, histopathological study was carried out, the anti-inflammatory mediators and the antioxidant potential in the liver tissues were evaluated. In addition, the total ethanolic extract of Dypsis lutescens leaves was subjected to different chromatographic separation techniques to yield ten phenolic compounds. The isolated compounds structures were spectroscopically elucidated. Results: Hepatoprotective activity of Dypsis lutescens ethanolic extract was estimated for the first time and showed significant activity against histopathological changes induced by D-galactosamine in liver. The extract improved the liver functions. Compared to the D-galactosamine group, the architecture of the liver in the treated groups was improved in the histopathological examination. These results proved the hepatoprotective activity of Dypsis lutescens and its ability in attenuating liver oxidative damage and inflammation. Phytochemical investigations of the total extract afforded ten compounds from the genus Dypsis. Conclusions: The alcoholic extract of Dypsis lutescens exerted potential hepatoprotective action, maintaining liver health and functions.

Neuroprotection by misoprostol against rotenone-induced neurotoxicity in rat brain

Objective:To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats.Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of 10, 100 or 1 000 μ g/kg. Rats were evaluated for brain lipid peroxidation (malondialdehyde: MDA), reduced glutathione (GSH), nitric oxide (NO) levels, and paraoxonase-1 (PON-1) activity. The concentrations of the anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase (iNOS) in the cerebral cortex and striatum were also performed.Results:Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation (MDA) by 61% (P<0.05) accompanied by an increase in NO by 73.1% (P<0.05) and a decrease in GSH concentration by 29.4% (P<0.05). In addition, brain PON-1 activity significantly decreased by 63.0% (P<0.05) and striatal Bcl-2 significantly decreased by 27.9% (P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation. Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum. Treatment with misoprostol at doses of 100 and 1 000 μ g/kg resulted in decreased brain MDA (by 16.5%-23.0%) (P<0.05) and NO levels (by 37.1%-40.7%) (P<0.05) and increased GSH concentrations (by 18.8%-30.1%) (P<0.05). PON-1 activity was significantly increased by 80.0%-114.8% (P<0.05) by misoprostol at 100 and 1 000 μ g/kg, respectively. In addition, misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats.Conclusions:These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.

Neuroprotection by misoprostol against rotenone-induced neurotoxicity in rat brain

Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods: Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of 10, 100 or 1 000

Amoxicillin–clavulanic acid induced sperm abnormalities and histopathological changes in mice

Objective To explore the genotoxic potential and histopathological changes induced in liver, kidney, testis, brain and heart after using the antibiotic drug amoxicillin/clavulanic acid (4:1). Methods The study included chromosomal aberration analysis in bone-marrow and mouse spermatocytes, induction of sperm morphological abnormalities and histopathological changes in different body organs. The drug was administrated orally at a dose of 81 mg/kg body weight twice daily (Total = 162 mg/kg/day) for various periods of time equivalent to 625 mg/men (twice daily). Results The results revealed non-significant chromosomal aberrations induced after treatment with amoxicillin/clavulanic acid (AC) in both bone marrow and mouse spermatocytes after 7 and 10 days treatment. On the other hand, statistically significant percentages of sperm morphological abnormalities were recorded. Such percentage reached 8.10 ± 0.55, 9.86 ± 0.63 and 12.12 ± 0.58 at the three time intervals tested (7, 14 and 35 days after the 1st treatment respectively) (treatment performed for 5 successive days) compared with 2.78 ± 0.48 for the control. The results also revealed histopathological changes in different body organs after AC treatment which increased with the prolongation of the period of therapy. Congestion of central vain, liver hemorrhage and hydropic changes in hepatocytes were noticed in the liver. Degenerative changes were found in kidney glomerulus and tubules while testis showed atrophy of seminiferous tubules, and reduction of spermatogenesis. AC also induced neurotoxicity and altered brain neurotransmitter levels. Hemorrhage in the myocardium, disruption of cardiac muscle fibers and pyknotic nuclei in cardiomyocytes were recorded as side effects of AC in heart tissue. Conclusions The results concluded that AC treatment induced sperm morphological abnormalities and histopathological changes in different body organs. Clinicians must be aware of such results while describing the drug.

relevance of Ki-67 and COX-2 immunoexpression in right-sided versus left-sided sporadic cancer colon in Egyptian patients

Cancer colon is one of the most common malignancies in Egypt. There are growing amount of data suggesting that carcinomas of the right and left colon should be considered as different tumor entities. Difference in tumor proliferation rates has been used as a prognostic tool. Ki-67 is a proliferation-associated nuclear and nucleolar protein antigen, which is expressed in all cycling cells, and it is an important marker to determine the degree of tumor malignance and invasion ability. Cyclooxygenase-2 [COX-2] is an important key enzyme required for the synthesis of prostaglandins, with high level seen in many cancers including colon cancer. A total of 167 colectomy specimens were reviewed during the period of 1 year. Fifty cases from the originally viewed 167 cases were chosen; 25 cases from the right-side colon and 25 from the left-side colon of comparable stages and grades. Each case was stained immunohistochemically for Ki-67 and COX-2 antibodies. The results of Ki-67 immunostaining showed that the difference between the right and left cases was significant [P < 0.05] in addition to the results of COX-2 immunostaining. We suggest that right and left cancer colon may be two different entities with possible different risk factors and different pathogenesis, and hence each may require different treatment polices as well. COX-2 expression in right-side tumors more than in left-side tumors may provide a chance for right-side cancers to benefit from COX-2 inhibitor therapy

Efficacy of some herbal preparations as hepatoprotective agents

In folk medicine, there are many herbal preparations used for their hepatoprotective activities. One of the most common recipes consists of equal parts [w/w] of decoction of [10% concentration]: Peumus boldus [leaves], Cichorium intybus [root] and Nigella sativa [seed] [Recipe 1]. Glycyrrhiza labell rhizome [root] replaced Cichorium intybus in [Recipe 2] or added to the Recipe 2 to form [Recipe 3]. Three groups of normal albino rats were orally administered 1.5 ml / 100 g of Recipe 1 [group 1], Recipe 2 [group 2] or Recipe 3 [group3] and the control group [group 4] was given 1.5 ml/ 100 g distilled water daily for 30 successive days. Results for normal groups of rats revealed that Recipe 1, Recipe 2 and Recipe 3 decreased plasma gamma-glutamyl transferase [GGT]: by -6.1, -26.7, -31.5%; ALT: by-3.8,-13.2, 17.6%; AST: by-5.9,-6.8-21.5%; triglycerides: by 1.8, 0, -13%; cholesterol: by -2.4, -1.2, -1.9% and, increased sleeping time: by 0.5, 1.4 and -0.9%, respectively, vs. control values. Second set of experiments, three groups of carbon tetrachloride-hepatic damaged rats were given the three recipes in the same above mentioned oral doses 2 weeks before carbon tetrachloride and continued for another 2 weeks after induction of the hepatic damage. A fourth group received CC14 for 4 weeks and served as control. The results indicated that there were significant decreases in GGT: [-70, -74.5, -82.0%]; ALT: [-30.1, -36.8, - 49.0%]; AST: [-9.9, -33.3, -43.8%]; triglycerides: [-11.8, -10.5, -17.0%]; cholesterol: [-17.4, -16.4, -24.4%] and sleeping time: [-24.0, -25.1, -37.9%], respectively, vs. carbon tetrachloride-hepatic damaged rats. Histopatholgical study revealed that the three recipes exhibited greater hepatoprotective effects in CCl[4]-induced liver injury by preventing development of hepatic lesions, including liver centrilobular inflammation, cell necrosis, fatty change, ballooning degeneration as compared to the 4[th] control group CCl[4]- intoxication. Also there was an improvement of hepatocytes- DNA contents. The modified recipe 3 was found to be more potent than recipe 1 or 2

Evaluation of the influence of each of melatonin and chromium against diabetes-induced alteration in the testis of albino rats using light and electron microscopies

Diabetes mellitus is a global disabling and deadly disease found world-wide. Altered testicular structure and function have been observed in diabetic human and animal models of diabetes with impaired reproductive function. The testicular atrophy and infertility were common in untreated or poorly controlled diabetics. The present study was carried out to compare the protective effect of melatonin and chromium against testicular alterations in alloxan-induced diabetes in albino rats. Thirty-five adult male albino rats were used in this study. The animals were divided into two main groups [each five]: non diabetic and diabetic rats, the first group was subdivided into 3 sub-groups: normal control, melatonin-treated animals and chromium-treated animals. The second group was subdivided into 3 sub-group [each five]: diabetic, diabetic rats treated with chromium, and diabetic rats treated with melatonin. Diabetes was induced by a single intra-peritoneal injection of alloxan monohydrate in dose of 60 mg/ kg body weight [BW]. The experiment was carried for forty-two days. Computer image analysis was used to measure the thickness of the basement membranes of the seminiferous tubules, the perimeter of the seminiferous tubules and the number of Leydig cells. In diabetic rats the seminiferous tubules showed statistically significant decrease in diameter, irregular outline and deformed shape because there was degeneration and disappearance of germ cells from many tubules. There was significant thickening of the basement membrane of the seminiferous tubules also detected. Ultrastructurally, nuclei of germ cells showed rarefied chromium and separated areas of nuclear envelop. Spermatids showed abnormal condensed nuclear chromatin surrounded by membranes with focal areas of discontinuity together with vacuolation of Sertoli cell cytoplasm. Melatonin and chromium improved the diabetic alteration in the basement membranes, diameter of the seminiferous tubules and the number of Leydig cells but they did not return to the control values. The improvement with melatonin was more than that with chromium. From the present study, it could be concluded that, melatonin and chromium showed a protective effect on histological alterations of the testis of alloxan-induced diabetes in rats