The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats

OBJECTIVE@#To investigate the protective effect of Thymus vulgaris (T. vulgaris) leaves 70% alcoholic extract against alcohol-mediate hepatotoxicity rats.@*METHODS@#The protective effect of T. vulgaris extract was investigated at dose of 500 mg/kg/day (as 0.1 of LD) orally against alcohol-mediate hepatotoxicity using adult male Wister albino rats during 21 days. Protective effect of T. vulgaris extract was evaluated comparing with silymarin standard drug at recommended dose (25 mg/kg/day) orally for 21 days. Serum liver and kidney functions, serum lipid profile, liver antioxidant enzymes activities, liver glutathione concentration (GSH), liver oxidative parameters and histopathological study of liver and kidney were estimated to find out protective effect of T. vulgaris extract.@*RESULTS@#Alcohol-mediate hepatotoxicity rats (alcohol-control) showed hepatocytes distortion represented as marked increment on liver biomarkers; alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) activities, as well as pronounced reduction on total protein and its fractions albumin and globulin production corresponding to normal ranges. Oxidative stress status was appeared on alcohol-control evident as significant depletion on GSH concentration, antioxidant enzymes activities; catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione- S- transferase (GST) and glutathione peroxidase (GPx) recorded significant dwindling, concurrence with significant augmentation on oxidative stress parameters; malondyaldehyde (MDA) and hydrogen peroxide (HO) concentrations with respect to normal values. Serum lipid profile was affected by alcohol administration, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were significantly reduced, meanwhile high density lipoprotein cholesterol (HDL-C) was raised comparing to normal ranges. Co-administration of T. vulgaris extract with alcohol showed protective effect on hepatocytes manifested as remarkable minimizing on ALP, AST and ALT activities and marked increment on total protein, albumin and globulin production compared to alcohol-control. Amelioration was achieved on oxidative stress status on rats co-administrated T. vulgaris extract with alcohol. Accordingly, antioxidant enzymes activities; CAT, SOD, GR, GST and GPx were significantly magnified, while oxidative stress parameters; MDA and HO concentration were significantly lessened corresponding to alcohol-control. Also, lipid profile was markedly improved and risk ratio was lowered by T. vulgaris extract co-administrated in comparison with alcohol-control. All these obvious results were confirmed by histopathological examination, which illustrated that extract showed normalization of degenerated and fibrotic liver tissue as of alcohol-control.@*CONCLUSION@#T. vulgaris extract protected hepatocytes from damaging by alcohol reflecting improvement on liver performance and inhibition of oxidative stress status of liver. T. vulgaris extract appeared hepatoprotective, hypolipidemic and antioxidant activities on alcohol-mediate hepatotoxicity rats compared to silymarin.

The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats

Objective To investigate the protective effect of Thymus vulgaris (T. vulgaris) leaves 70% alcoholic extract against alcohol-mediate hepatotoxicity rats. Methods The protective effect of T. vulgaris extract was investigated at dose of 500 mg/kg/day (as 0.1 of LD

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

Protective effect of fish liver oil and propolis on anticonvulsant drugs-induced osteoporosis

Osteoporosis is a major health problem and its prevalence increases the risk of bone fracture. It is classified into primary [postmenopausal or age related] and secondary [related to chronic diseases, drug therapy, or life style]. There is accumulating evidence that patients on antiepileptic drugs [AEDs] are at an increasing risk of developing osteoporosis. The present study aimed at investigating the protective effect of dietary natural products, fish liver oil, and propolis on osteoporosis caused by anticonvulsant drugs. A total of 105 albino rats were used, divided into seven groups of 15 rats each. Group 1 was used as a control group. In group 2, rats were injected intraperitoneally with pilocarpine [300 mg/kg body weight]. The pilocarpine-induced epileptic rats in the other five groups were orally treated with valproate [400 mg/kg body weight], a combination of valproate and fish liver oil [0.4 ml/kg body weight/day], a combination of valproate and propolis [50 mg/kg body weight/ day], fish liver oil, and propolis, respectively. At the end of the experiment [6 months treatment], animals were sacrificed, femur shafts were extracted, decalcified, and processed into paraffin blocks for histopathological and image analysis and morphometric studies. Rats treated with the antiepileptic valproate alone showed a decrease in the thickness of shaft cortical bone, with a marked decrease in the number of osteocytes, increase in Haversian canals, and decrease in bone trabeculae, disruption of normal architecture, and widening of bone marrow spaces compared with the control group. Treatment with the dietary natural products, fish liver oil, and propolis along with the AED valproate might improve histopathological changes and morphometric parameters in bone associated with AED-induced osteoporosis

Vitamin C and E antagonistic effect for tamoxifen-induced rat liver damage: a histopathological, histochemical and ultrastructural studies

Tamoxifen is widely used to treat oestrogen dependent carcinoma of the breast. Previous long term studies have shown that oral administration of tamoxifen induces hepatoproliferative lesions and hepatocellular tumors in rats. This study was designed to evaluate the effects of tamoxifen on liver of rats and the possible protective effects of vitamin C and/ or vitamin E in amelioration of these effects. A total of 70 adult female albino rats were used in this study. The animals were divided into seven groups. Each group contained 10 rats. The rats of the first group were kept as control. Animals of the second group were daily dosed orally with tamoxifen 20 mg/ kg b. w. by stomach tube for two weeks. The third group was given vitamin C at dose level of 0.01 g/ 100 g b w by stomach tube, 15 min before daily administration of tamoxifen. The fourth group was given vitamin E at dose level of 100 mg/ kg b.w, 15 min prior to daily administration of tamoxifen throughout the whole period. The fifth group was given combination of the two vitamins [vitamin C and vitamin E] at dose level of 0.01 g/ 100 gb.w. and 100 mg/ kg b.w. respectively, 15 min before daily administration of tamoxifen for two weeks. Each of the remaining two groups was daily given vitamin C [0.01 g/ 100 g b.w.] and/ or vitamin E [100 mg/ kg b.w.] only for two weeks. Paraffin sections were used for the histopathological study. For the histochemical investigations, sections were stained to demonstrate DNA, mucopolysaccharides and protein content. Histopathological effects of tamoxifen were demonstrated in liver as vacuolar degeneration, fatty changes and hydropic degeneration. Signs of degeneration in the form of karyolysis and karyorrhexis were also seen. Moderate dilatation of blood sinusoids, some dysplastic cells and chromalin clumping could be observed. Quantitative DNA image analysis [Lecia image] showed a decrease in DNA content [hypoploidy] in liver of rats treated with tamoxifen only. Tamoxifen induced histochemical changes consisted of marked diminution of protein and mucopolysaccharides content. No histopathological, histochemical and ultra structural changes could be noticed in rats treated with vitamin C and, or vitamin E only. The treatment of rats with vitamin C and/ or vitamin E prior to tamoxifen resulted in amelioration of the histopathological changes of liver as well as histochemical and ultrastructural changes

Possible protective effects of vitamin E, alfa-lipoic acid and lycopene in mercuric chloride-induced nephrotoxjcity and hepatotoxjcity in rats

Mercury [Hg] is a commonly encountered environmental contaminant. It causes severe nephrotoxicity and hepatotoxicity. Although the mechanism underlying Hg toxicity is not clearly understood, several hypotheses encouraging the role of oxidative stress have been proposed. Consequently, the possible protective effects of three natural antioxidants namely vitamin E [VE, 100 mg/kg], alfa-lpoic acid [ALA, 50 mg/kg] and lycopene [LYC, 6 mg/kg] against nephrotoxicity and hepatotoxicity induced by a single i.p. administration of HgCl[2] [3.75 mg/kg] were examined in rats. Test agents were administered orally for 14 consecutive days prior to acute HG intoxication. Nephrotoxicity was assessed by measuring serum levels of urea, creatinine and uric acid, while hepatotoxicity was assessed by measuring serum activities of ALT and AST as well as histological examination of both kidney and liver tissue sections. Tissue reduced glutathione [GSH] and total thiols [SHs] contents were determined. The contents of thiobarbituric acid reactive substances [TBARS], as an index of lipid peroxidation, and total nitrate/nitrite [NO[x]], which reflects nitric oxide output, were also estimated. Acute Hg intoxication resulted in marked nephrotoxicity and hepatotoxicity accompanied by significant reduction in tissue GSH and SHs contents. Interestingly, Hg significantly reduced renal TBARS content, while significantly elevated that of liver. On the other hand, it significantly reduced hepatic NO[x] while did not affect that of kidney. Prior administration of VE, ALA or LYC did not prevent Hg-induced elevations in serum creatinine and urea nitrogen levels. However, pretreatment with ALA or LYC significantly increased Hg-induced decrease in serum uric acid. VE or ALA protected against elevation of both serum ALT and AST. LYC protected only against elevation of serum ALT. VE and ALA provided a significant protection against renal GSH depletion and hepatic THARS elevation, while LYC protected against only hepatic TBARS elevation. None of the test agents produced any significant protection against Hg-induced alterations in renal contents of SHs, TBARS and NO[x] and on hepatic contents of GSH, SHs and NO[x] It could be concluded that the use of antioxidants might protect against Hg toxicity, although mechanisms other than oxidative damage might also contribute to both renal and hepatic cellular injury induced by Hg

Effects of certain natural products in adjuvant-induced arthritis

The effects of curcumin [80 mg/kg; p.o.] and quercetin [50 mg/kg; p.o.],alone or combined, with diclofenac [2 mg/kg; i.p.] on adjuvant-induced arthritis in rats were studied and compared with diclofenac monotherapy. Experimental arthritis was induced by s.c. injection of 0.4 ml Freund's complete adjuvant [FCA] into the subplanter tissue of the right hind paw of all rats except the normal group [1% tween 80; p.o.]. The test agents were administered daily for 28 days starting from the 1[st] day of adjuvant inoculation. The control arthritic group received the vehicle [1% tween 80; p.o.] daily for the whole experiment period. Assessment of the anti-inflammatory effects of different treatments was done by measurement of paw volume before FCA injection and at different time intervals, for 28 days, thereafter using water plethysmometer. Collection of blood samples was carried out after the last paw measurement [day 28]. They were used for determination of serum lactate dehydrogenase [LDH] activity and levels of serum total antioxidants, tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], calcium [Ca[2+]] and nitrite, a stable metabolite of nitric oxide [NO] which reflects its level. In addition, the level of thiobarbituric acid reactive substances [TBARS], as an index of lipid peroxidation was also determined. Histopathological examination of paw tissues was also carried out. Injection of FCA into the hind paw of rats induced marked arthritis manifested by paw edema during the 28-day experiment period. Treatment with diclofenac alone markedly inhibited adjuvant-induced arthritis at all the studied time intervals. Curcumin, alone, reduced FCA induced edema at day 19 only and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at all the studied time intervals. Quercetin, on the other hand, reduced edema during the chronic phase of arthritis at days 19 and 28 and its combination with diclofenac antagonized the anti-inflammatory effect of the latter at day 11 only. FCA resulted in increased levels of serum TBARS, TNF-alpha, IL-1beta and nitrite as well as increased serum LDH activity. Whereas, no significant changes on serum total antioxidants or Ca[2+] levels were noted. Treatments with curcumin or quercetin alone or combined with diclofenac attenuated most of the biochemical changes elicited by FCA. Histopathological examination of paw tissues showed marked vacuolar degeneration and degradation of articular surfaces by FCA injection. Diclofenac and curcumin, alone or combined together, markedly attenuated FCA-induced histopathological changes. On the other hand, quercetin alone or in combination with diclofenac was less protective. In conclusion, the effect of diclofenac monotherapy was still superior compared to curcumin and quercetin. Effects of curcumin and quercetin seem to be mediated through influences on production of pro-inflammatory cytokines, NO level as well as lipid peroxidation

Postnatal growth and development of skeletal muscle fibers in albino rat. A histological and histochemical study

This work was done to study the postnatal development of the skeletal muscle fibers, which have received little attention in the few last decades, regarding their morphological and histochemical features. The gastocnemius muscle of fifty albino rats of different ages were examined histologically using H and E and Van Gieson's stain to study the morphological features of the developing skeletal muscle. This reveals that the skeletal muscle fibers, since birth, were enclosed by three levels of connective tissue containing blood vessels and nerves, which increase in amount with the advance of age. The nuclei were distributed irregularly throughout the skeletal muscle fiber during the first week of life, and then they take a peripheral position. The transverse striations of the skeletal muscle fibers couldn't be seen until 14[th] days of age of albino rat. The histochemistry of the developing skeletal muscle was investigated using Periodic acid Schiff reagent, Nitroblue tetrazolium technique for the detection of succinic dehydrogenage activity and Tetrazolium reductase linked staining technique for the detection of alpha-glycerophosphate dehydrogenase activity. This revealed that the gastrocnemius muscle displayed increasingly glycolytic fast fibers profile with the advance of age. According to succinic dehydrogenase activity the muscle could be differentiated since birth into 2 types of fibers: Type 1 [slow oxidative fibers] and Type II [fast glycolytic fibers]. From 14[th] days postnatally a third type of fibers, Type III [fast oxidative glycolytic fibers] could be recognized. Differentiation of both types of skeletal muscle fibers [slow and fast twitch] according to alpha-glycorophosphate dehydrogenase enzyme activity could be made from the beginning of the first week of life, whereas the appearance of the third type of fibers[fast oxidative glycolytic fibers] was delayed till the third week of life. As regard the glycogen content, the skeletal muscle fibers in younger age groups contained more glycogen than in adults and differentiation between fast and slow twitch fibers based on this point could be made at the end of the first week postnatally. It is concluded that the skeletal muscle in albino rat was undeveloped at birth and its growth and differentiation was a gradual process including major changes in both morphological and histochemical features

In vivo effect of cinnarizine on acute hepatic damage in mice

This study aimed to investigate the effect of cinnarizine, a drug used for the treatment of motion sickness and which has direct anti-dopaminergic features [Dopamine Dl and D2 receptor blockade], on the acute hepatic injury in mice. Hepatotoxicity was induced by CCI4 orally [0.28 ml/100 g given twice with one week apart]. Cinnarizine at three dose levels [5, 10 or 20 mg/kg] or silymarin [22 mg/kg] were given orally daily for 14 days. starting at the time of administration of CCI4. Liver damage was assessed by determining liver serum enzyme activities and by hepatic histopathology. Cinnarizine decreased the increases in serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP] and also prevented the development of hepatic necrosis caused by CCI4. The effect of cinnarizine was a dose-dependent one. Cinnarizine administered at 10 or 20 mg/kg caused significant reduction in the elevated plasma ALT by 32.7, 34.3%, AST by 18.8, 34.7% and ALP by 32.8, 42.9%, respectively. In comparison, the elevated serum ALT, AST and ALP levels were decreased by 42.1%, 37.9% and 43.4% of controls, respectively by 22 mg/kg of silymarin. Histopathologic examination of the livers of CCI4-treated mice administered cinnarizine at 20 mg/kg showed marked restoration of the normal architecture of the liver tissue with minimal fibrosis. It is concluded that administration of cinnarizine in a model of liver injury induced by CCI4 results in less liver damage

Nephrotoxicity induced by long-term administration of paraquat in rats: protective effects of quercetin and extracts of malt and green tea

Paraquat [PQ], a well-known herbicide, causes nephrotoxicity mediate by redox-cycling and extensive production of superoxide anions in the kidney. The possible protective effects of three natural products namely; green tea extract [I mg/kg], malt extract [625 mg/kg] and quercetin [50 mg/kg], against nephrotoxicity induced by long-term administration of PQ in rats were examined. PQ was intraperitoneally injected once weekly [20 mg/kg] with or without oral daily treatment with any of the three agents for 6 consecutive weeks. Nephrotoxicity was assessed by measuring serum creatinine level, histological examination of kidney sections and calculation of percentage kidney-to-body weight of rats. In addition changes in enzymatic activities of superoxide dismutase [SOD], lactate dehydrogenase [LDH] and myeloperoxidase [MPO], as well as reduced glutathione [GSH], protein thiols [Pr-SHs] and total nitrate/nitrite [NOx] contents of renal tissues were determined. Renal lipid peroxidation was also assessed by measurement of the levels of thiobarbituric acid reactive substances [TBARS]. PQ administration resulted in marked nephrotoxicity manifested by severe increase in serum creatinine level accompanied by changes in renal oxidant status of rats demonstrated by elevated TBARS level and increased activities of MPO and SOD. PQ also resulted in depletion of renal GSH and NOx contents as well as reduced activity of cytosolic LDH. On the other hand, no significant effect was noted on percentage kidney-to-body weight of rats or on renal Pr-SHs contents. Six weeks of regular daily treatment with any of the chosen agents significantly protected against most of PQ-induced biochemical changes. Histological examinations of kidney morphological changes revealed marked lesions with PQ especially in renal proximal tubules and variable degrees of protection by the test agents with the best results produced by malt extract and quercetin and to lesser extent by green tea extract. It could be concluded that malt extract and quercetin offered remarkable protection against PQ-induced nephrotoxicity in rats. Green tea extract produced some beneficial effects on the biochemical events associated with PQ-induced nephrotoxi city

Role of some antioxidants in protection from the structural damage produced in the stomach and intestinal mucosa of diabetic rats. Histological and histochemical studies

Diabetes Mellitus affects the structural and functional integrity of many organ systems. Only a few previous studies have discussed these effects on the stomach and small intestine. In the present study, the effects of Alloxan-induced diabetes as well as the effect of some antioxidants [melatonin, chromium, a-tocopherol, ginseng and green tea] in reducing these effects on the mucosa of both stomach and small intestine were investigated. The morphological examination of the stomach and intestinal mucosa in diabetic rats revealed the presence of marked erosion and necrosis of mucous neck cells and parietal cells, while peptic cells showed vacuolar degeneration. The lining epithelial cells of the villi of the small intestine showed severe degeneration with marked hypertrophy and swelling of goblet cells. The tunica propria showed diffuse inflammatory cellular infiltration. Examination of the mucopolysaccharide content in these specimens using PAS reaction revealed a decrease in the positivity of the reaction in the luminal surface of epithelial cells of diabetic rats as compared with control non-diabetic rats, but an intense reaction in the gastric pit cells. Examination of intestinal mucosa revealed marked increase in goblet cells' reaction. Examination of the protein content in the same specimens using bromophenol blue stain showed vacuolar degeneration which was observed in the epithelial cells of both stomach and small intestine accompanied by decreased protein content. Examination of the stomach and small intestinal mucosa of diabetic rats treated with antioxidants, revealed marked improvement and normalization of the luminal surface of epithelial cells and gastric mucosal cells. There were detectable repair of the villus epithelium of the small intestine and normalization of the PAS positive reaction and protein content in both stomach and intestinal mucosa