Effect of silymarin mixed with Dimethyl Dimethoxy Biphenyl Dicarboxylate versus silmarin alone in liver of rats treated with carbon Tetrachloride

This study aimed to investigate the effect of a combination of silymarin and dimethyl dimethoxy biphenyl dicarboxylate [Mepacure] versus silymarin alone on the development of acute hepatic injury caused in the rat by the administration of CCLi in vivo. Mepacure at doses of 8.4, 16.8 and 25.2 mg/kg containing mixture of silymarin at doses of 5.2, 10.4 or 15.6 mg/kg and dimethyl dimethoxy biphenyl dicarboxylate [DDP] at doses of 3.2, 6.4 or 9.6 mg/kg, respectively, or silymarin alone at a dose of 22 mg/kg were given once daily orally simultaneously with CCU and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activity and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerised image analyzer. The combination of silymarin and DDP administered to CCL4 treated rats at the above doses, resulted in a dose-dependent decrease of elevated alanine aminotransferease [ALT] by 27.5, 30 and 35%, aspartate aminotransferase [AST] by 10.3, 34.7 and 45% and alkaline phosphatase [ALP] levels by 10.8, 15.7 and 33.4%, respectively. Meanwhile, silymarin administered alone, reduced the elevated ALT, AST and ALP levels by 28, 39.4 and 14.2%, respectively. Total proteins in serum were reduced in CCL4 treated rats by 33.3% compared with normal rats. In CCL4 treated rats, proteins in serum increased after the combination of silymarin and DDP by 16.4-18.8%. Meanwhile, silymarin alone increased serum proteins by 27% compared with CCL4 treated control rats. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in rats treated with the combination of silymarin and DDP or with silymarin alone compared with CCL4 rtreated control rats. Quantitative analysis of the area of damage showed a 93.8% reduction in the area of damage in CCL4 treated rats after treatment with silymarin alone and 56.3, 72.8 and 81.3% reduction after the combination of silymarin [5.2, 10.4 or 15.6 mg/kg] and DDP [3.2, 6.4 or 9.6 mg/kg], respectively. Data in the present study indicates that DDP potentiates the protective effect of silymarin on hepatic injury caused by CCL4 in rats

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

Ductal breast tumours: mean nuclear area and metallothionein expression in correlation with estrogen receptor status

Estrogen is an important growth Ilictor for breast tumour playing an important role in regulating the proliferation and differentiation of normal and malignant mammary epithelial cells. Nuclear morphometry and Metallothioneins [MTs] are indicators of proliferation that have been used as predictors of prognosis in many tumours. The present study aimed to study mean nuclear area and MT; ER expression in fibroadenoma, ductal carcinoma in situ and infiltrating ductal carcinoma of the breast. Also MNA and MT expression will be correlated with histologic grade and ER status in breast carcinoma. Breast tissues from 12 patients with fibroadenoma [FA], 6 patients with ductal carcinoma in situ [DCIS] and 20 patients with infiltrating durtal carcinoma [IDC] were used in this study. Mean nuclear area [MNA] and metallothionein [MT] expression; as proliferation markers; were investigated and correlated with estrogen receptor [ER] status. All cases of fibroadenoma, 4 out of 6 cases [66.7%] of DCIS and 12 out of 20 cases [60%] of IDC were positive for ER. MNA of cancer cells was significantly larger than that of normal and benign breast tissue. A significant direct correlation was found between MNA and histologic grades. MNA of ER negative carcinomas was significantly larger than that of ER positive tumours. In normal and benign breast tissue, myoepithelial cells consistently expressed the MT protein. Two out of 6 DCIS cases [33.3%] and 13 out of 20 cases of IDC cases [65%] were positively stained for MT. MT positivity was directly correlated with histologic grade of JDC. There was a highly significant inverse correlation between MT and ER over-expression. From this study, it is concluded that in invasive ductal carcinoma of the breast, the large MNA and MT over-expression are correlated with histologic grades and ER negativity. Therefore, MNA and MT overe-expression may be possible important indicators for more aggressive and less differentiated breast carcinoma

modulatory effect of some antioxidants on hepatocytes of adriamycin treated rats: light and electron microscopy study

Adriamycin [ADR] is one of an anthracycline group. It is used as an effective chemotherapeutic agent in treatment of many human tumors. However, its clinical use has been limited because of its severe toxicity to the heart, liver, kidney, stomach, intestine and bone marrow. On the other hand, L-carnitine and b-carotene have high antioxidative properties. This study was an attempt to evaluate the possible protective effect of L-carnitine and b- carotene against the [ADR] induced hepatotoxicity. Thirty six adult male albino rats weighing 150 +/- 180 gm were divided into four groups. Group I: the control group. Group II: each rat received four equal intraperitoneal injections of ADR [each containing 2.5 mg/kg] over two weeks. Group III: each rat received ADR plus daily oral intake of 200 mg/kg of L-carnitine and group IV: which was given ADR plus daily oral intake of 30 mg/kg of B- carotene. One day after the last dose all animals were sacrificed and their livers were dissected. Liver specimens were prepared for both light and electron microscopy. At light microscopic level, paraffin sections were subjected to Hx and E., Feulgen reaction for DNA and bromophenol reaction for total protein contents. Light microscopic examination of group II rats revealed loss of normal hepatic architecture. Most hepatocytes showed vacuolated cytoplasm. Pyknotic, fragmented, ghost and totally absent nuclei were also observed. Many necrotic cells were present. Significant decrease in nucleic acid and total protein contents was found as a result of [ADR] treatment. At the ultrastructural level, the hepatocytes exhibited nuclear chromatin condensation, swelling of the mitochondria with destructed cristae. Massive dilatation of rER and sER and Golgi apparatus was also noticed. Many electron dense cytoplasmic bodies suggested to be lysosomal elements were found. On the other hand, animal groups treated with L- carnitine and b- carotene exhibited that most of hepatocytes were apparently normal with minimal cytoplasmic vacuolation. Marked improvement in the DNA and total protein contents. Ultrastructurally, mitochondria were slightly destroyed Minimal rER, sER, and Golgi dilatation and there was homogenous nuclear chromatin distribution. Thus, L-carnitine and b- carotene could ameliorate ADR hepatic alterations and their supplementation is recommended for cancer patients treated with [ADR]

protective role of ginseng against liver damage caused by potassium dichromate Cr [IV]: light and electron microscopic studies

Human exposure to carcinogenic Hexavalent Chromium Cr [VI] compounds is found among workers in a large number of professional groups, and it can also occur through environmental pollution. A significant number of toxic waste sites contain Cr as a major contaminant. Chromium is a heavy metal which is widely used in the painting, pigments, dyes, and leather tanning industries. Ginseng is one of the most popular herbal remedies. In a series of experiments we have studied the possible role of the water ginseng extract, in modulating the histological and histochemical damage induced by potassium dichromate Cr [VI] in liver tissue of albino rats. Fourty male albino rats were used in this study. Potassuim dichromate was given orally in a dose of 50mg/kg body weight. Rats were treated orally with ginseng extract in a dose of 20 mg/kg body weight. Specimens of the liver were taken and prepared for light and electron microscopic investigations. Other specimens were stained with, periodic-shiff reagent and Feulgen stain for histochemical investigations. The morphometric analysis of hepatocytes nuclear diameters, the optical density of mucopolysaccharide and DNA reactions were evaluated by the computer image analysis. Light microscopic investigation of liver of rats treated with Cr [VI] showed massive vacuolar degeneration and circumscribed nodule formed of a homogenous acidophilic material infiltrated by mononuclear cells. Apoptic cells with deep eosinophilic cytoplasm and small deeply stained [pyknotic] or fragmented nuclei were clearly demonstrated together with fatty degeneration manifested by round empty well-circumscribed spaces. Necrosis of hepatocytes was observed, they showed irregular nuclei densly packed with chromatin. At the ultrastructural level the hepatocytes revealed that endoplasmic reticulum was slightly swollen and vesiculated. In addition, different degrees of mitochondrial damage were present in the form of differences in shape and size and distortion of their ridges. The results have manifested a possible protective role of ginseng extract on the general cellular morphology, as well as significant improvement in glycogen and DNA contents in ginseng treated rats against chromium toxicity

Light and electron microscopic study on the effect of L-carnitine and B-carotene on the Doxorubicin toxicity in the heart and testes of albino rats

Doxorubicin [Dox] is an anthracycline antibiotic, with a wide spectrum of antitumor activity . Dox as a chemotherapeutic agent is highly toxic . L-carnitine and B-carotene have recently been shown to have high antioxidative properties. This study is an attempt to evaluate the heart and testes responses after Dox injection with or without exogenous L-carnitine or B-carotene protection . Male albino rats, body weight 150-180gm, were divided into nine groups : cont. Dox [therapeutic dose], carnitine, carotene, carnitine plus Dox, carotene plus Dox, Dox [single dose], Dox [single dose] plus carnitine, Dox [single dose] plus carotene .Dox was injected I. P. at a therapeutic dose of 2mg/Kg/b.w. [twice weekly for two weeks], and as a single dose of 15 mg/kg /b.w. Carnitine and carotene were administered I. P. at a dose of 200 mg/kg b.w. and 30 mg/kg b.w. respectively . The experimental period was two weeks . One day after the last dose, the animals were sacrificed and their hearts and testes were dissected . Testicular and cardiac damage were determined histologically and histochemicaly by light and transmission electron microscopes .Dox induced cardiac damage manifested as vacuolar and fatty degeneration, interstitial fibrosis and loss of myoflbrils. Ultrastructurally variation in mitochondrial size and shape with destruction and vacuolization were noticed. On the other hand, Dox induced testicular alterations consisting of cytoplasmic vacuolization, spermatocytes fragmentation and necrosis with large vacuoles in the seminiferous epithelium. Ultrastructurally spermatocytes exhibited ill defined plasma membrane, damaged mitochondria and increase in myelin figure together with abnormal sperms. The histochemical investigations revealed a relative decrease in DNA, protein and PAS reactions, in the cardiac myocytes and in the spermatogenic and interstitial cells of Dox treated rats . However, these alterations became less severe in the protected groups, in both heart and testes suggesting L- Carnitine and B- Carotene as possible protectors against Doxtoxicity

Protective effect of melatonin, methionine and zink on cadmium nephrotoxicity: histopathologically, histochemically and AgNORs quantitation

Cadmium [Cd] is a highly toxic heavy metal that is naturally present in the environment. Chronic exposure to Cd causes hepatotoxicity and nephrotoxicity. The present study aimed to study the protective effect of melatonin, methionine and zinc against histopathological, histochemical and proliferative effects of cadmium on the kidney of rats. A total of 80 female albino rats were included in this study and divided into 8 groups. They were injected intraperitonealy with cadmium chloride [CdCl2] [2 mg / kg b.w.], melatonin [10 mg / kg b.w.], methionine [42.8 mg / b.w.] or zinc [20 mg / kg b.w.] with or without CdCl2 daily for 10 days. Treatment with CdCl2 induced marked tubular cell degeneration with large areas of interstitial hemorrhage.There were marked destruction of the brush borders with decrease in glycogen and protein contents of the degenerated tubules. AgNORs count significantly increased. Injection of melatonin or methionine to CdCl2 treated rats resulted in improvement of Cd-induced histopathological and histochemical changes. AgNORs count significantly decreased. Zinc injection partially protected the kidney from Cd-induced effects. In conclusion, melatonin and methionine have a more protective effect than zink against Cd nephrotoxicity