scholarly journals CIRRHOSIS OF THE LIVER CAUSED BY EXCESS DIETARY CYSTINE

1941 ◽  
Vol 73 (2) ◽  
pp. 161-172 ◽  
Author(s):  
David P. Earle ◽  
Joseph Victor
Keyword(s):  
Fatty Infiltration ◽  
Cirrhosis Of The Liver ◽  
Cellular Damage ◽  
Albino Rats ◽  
Renal Lesion ◽  
Stock Diet ◽  
Hepatic Cells ◽  
Acute Lesion ◽  
Hemorrhagic Necrosis ◽  
Mitotic Figures

1. Cystine fed to young albino rats as 10 per cent of the diet resulted in: (a) Portal hemorrhagic necrosis, resembling eclampsia, within 3 or 4 days. (b) A high mortality rate. (c) Fatty infiltration of hepatic cells in all rats surviving the initial acute lesion. (d) Cirrhosis of the liver in rats surviving more than 2 weeks. 2. 5 per cent dietary cystine produced marked fatty infiltration of the liver, followed by portal hemorrhagic necrosis. Cirrhosis was present in one of the two rats on the diet for 6 weeks. 3. The livers of rats fed 5 or 10 per cent cystine diets followed by the McCollum stock diet, showed evidence of residual cellular damage, and of regeneration as shown by mitotic figures. 4. In this series of 30 rats on excess dietary cystine, a renal lesion was found in only one case.

scholarly journals EFFECTS OF EXCESS DIETARY CYSTEIC ACID, dl-METHIONINE, AND TAURINE ON THE RAT LIVER

1942 ◽  
Vol 76 (4) ◽  
pp. 317-324 ◽  
Author(s):  
David P. Earle ◽  
Katharine Smull ◽  
Joseph Victor
Keyword(s):  
Carbon Chain ◽  
Cirrhosis Of The Liver ◽  
Cysteic Acid ◽  
Albino Rats ◽  
Amino Group ◽  
Liver Lesions ◽  
Stock Diet ◽  
Liver Necrosis ◽  
Low Fat Diet ◽  
Low Protein

1. Cysteic acid fed to albino rats as 12.5 to 15 per cent of the McCollum stock diet caused portal necrosis and cirrhosis of the liver within 2 weeks. Concentrations of cysteic acid of 6.25 per cent or less in the diet produced no liver lesions within 2 weeks. 2.dl-Methionine fed as 6.4 to 12.4 per cent of the McCollum stock diet or of a low protein, low fat diet, resulted in severe atrophy of the liver cells but no cirrhosis of the liver. 3. Taurine fed as 1 to 10 per cent of the McCollum stock diet produces no liver lesions. 4. For reasons discussed in the paper, it is concluded that the liver necrosis and cirrhosis produced by cystine and cysteic acid are not dependent upon the S-S linkage of the cystine, the oxidation of the sulfur, the formation and excretion of large amounts of urinary sulfate, or the presence of an amino group separated from a sulfur molecule by a 2 carbon chain.

scholarly journals Biochemical, Histopathological and Mutagenic Changes Following the Co-administration of Antihelminthic and Antimalarial Drugs in Wistar Rats

2019 ◽  
pp. 1-12
Author(s):  
A. A. Obiajunwa ◽  
E. T. Idowu ◽  
O. A. Otubanjo
Keyword(s):  
Body Weight ◽  
Treatment Group ◽  
Fatty Infiltration ◽  
Portal Tract ◽  
Renal Tissue ◽  
Albino Rats ◽  
Male Adult ◽  
Treatment Groups ◽  
Combination Treatments ◽  
Therapeutic Doses

Aim: To determine the effects of antimalaria and antheminthic drugs combination in the incidence of histopathological alteration and biochemical modulations in liver and kidney of albino rats. Place and Duration of Study: The study was undertaken at the Zoology Department University of Lagos Akoka Lagos Nigeria. Methodology: A total of twenty (25) Male adult albino rats of 13-15 weeks old were divided into 5 groups of 5 rats each and daily oral administration of human therapeutic doses of praziquantel (PZQ 50 mg/kg body weight) separate and in combination with ivermectin (IVM 0.4 mg/kg body weight), albendazole (ALB 15 mg/kg body weight) and Artemether-lumefanthrine (ACT 140 mg/kg body weight) was administered with the  group which serve as the control receiving 1ml distilled water. Toxic effects due to these treatments were investigated using histopathological, biochemical and mutagenic indices at day 8th and 15th of the study. Results: Biochemical assessment revealed significant reduction in AST, ALT, ALP and potassium in the treatment group compared to the control. Increase in the level calcium, Albumin and bicarbonate were also observed in treatment groups. Histopathological assessment of the liver showed a general incidence of focal inflammation along the portal tract area, but did not show any differential severity across treatment groups except for single PZQ treatment group which were characterized by fatty infiltration. A general occurrence of mesangial damage and glomerula injury was observed in kidney tissues. Renal lesions were more severe in single PZQ + IVM treatment groups while mild lesions characterized renal tissue from PZQ+ACT treatment groups. Mutagenic effects as indicated by the high incidence of sperm head abnormalities was recorded across combination treatments especially in PZQ+ IVR and PZQ+ ACT groups. Conclusion: Findings suggest that combination therapies are synergistic and could result in nephrotoxicity, antidiuretic effects, dehydration and mutagenicity at human therapeutic doses.

scholarly journals Development of a Phototoxicity Testing Strategy for Accurate Photosafety Evaluation of Pharmaceuticals Based on the Assessment of Possible Melanin-Binding Effects

2018 ◽  
Vol 37 (4) ◽  
pp. 296-307
Author(s):  
Jelle Reinen ◽  
Pieter van Sas ◽  
Ton van Huygevoort ◽  
Leticia Rubio ◽  
Kevin Scase ◽  
...  
Keyword(s):  
Cellular Damage ◽  
In Vivo Studies ◽  
Brown Norway ◽  
Albino Rats ◽  
Guidance Document ◽  
High Affinity ◽  
Drug Concentrations ◽  
Melanin Binding

Drug-induced phototoxicity occurs when drugs absorb natural sunlight, leading to chemical reactions causing cellular damage. Distribution to light-exposed tissues is critical and is enhanced by binding to melanin. The International Council on Harmonization S10 guidance document on photosafety evaluation of pharmaceuticals states that although nonpigmented skin tends to be more sensitive than pigmented skin, pigmented skin models should be considered for drugs that bind significantly to melanin. In this study, an in vitro melanin-binding assay was evaluated as prescreening tool for animal model selection. Binding of various structurally diverse phototoxic drugs to synthetic melanin was investigated in vitro and the high-affinity binder sparfloxacin (SPX), moderate-affinity binder 8-methoxypsoralen (8-MOP), and low-affinity binder pirfenidone (PIF) were selected for in vivo studies. Pigmented Brown Norway (BN) rats were compared with nonpigmented Wistar Albino rats to evaluate their sensitivity for the assessment of phototoxicity and skin concentrations of the drugs were measured. For SPX, the onset of phototoxic symptoms was faster for BN rats and drug concentrations were significantly higher in skin of BN rats. For 8-MOP, both models showed comparable sensitivity and skin concentrations did not differ. For the low-affinity binder PIF, no phototoxic effects were observed and skin concentrations in both models were similar. A combined in vitro/in vivo approach was developed that can be applied for accurate photosafety evaluation of pharmaceuticals based on the assessment of possible melanin-binding effects. In view of the presented data, the pigmented model could be considered for compounds showing a high-affinity binding capacity in vitro.

Short term chronic toxicity of tributyltin on the testes of adult albino rats and the possible protective role of omega-3

2020 ◽  
pp. 096032712094745
Author(s):  
Marwa G Ahmed ◽  
Mona El-Demerdash Ibrahim ◽  
Hoda R El Sayed ◽  
Samah M Ahmed
Keyword(s):  
Treated Group ◽  
Toxic Effects ◽  
Cellular Damage ◽  
Antioxidant Defenses ◽  
Control Group ◽  
Albino Rats ◽  
Omega 3 ◽  
Group I

The declining rate of male fertility is a growing concern. Tributyltin (TBT) is a well-known endocrine disruptor (ED), that induces imposex in female gastropods and is widely used in various industrial applications. The aim of this study was to evaluate the toxic effects of TBT on the testes of adult albino rats and the possible role of omega-3. Forty two adult male albino rats were divided into five groups; control group (Group I) and four experimental groups: omega-3 treated group, TBT treated group, TBT & omega-3 treated group and follow up group. At the end of the study, the rats were subjected to biochemical, histological, immunohistochemical staining for Ki-67 and seminal examinations. Our results clarfied that TBT induced a significant decrease in testosterone, FSH, LH and serum glutathione peroxidase levels and a significant increase in the serum Malondialdehyde as compared to the control group. Tributyltin induced disorganization and shrinkage of seminiferous tubules, apoptosis, cellular damage and marked reduction in the germinal epithelium. A significant decrease in the cell proliferation and arrested spermatogenesis were also detected. Seminal analysis of TBT group showed a significant affection of all parameters as compared to other groups. Omega-3 ameliorated all of these hazardous effects. Follow up group still showed toxic effects. In conclusion, TBT has a toxic effect on the testis. Increased testicular oxidative stress, cellular damage and arrest of spermatogenesis with attenuation in antioxidant defenses are all contributing factors. Omega-3 can protect against TBT induced reproductive toxicity.

scholarly journals Antioxidant and Anti-Apoptotic Properties of Oat Bran Protein Hydrolysates in Stressed Hepatic Cells

Foods ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 160 ◽  
Author(s):  
Ramak Esfandi ◽  
William G. Willmore ◽  
Apollinaire Tsopmo
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzyme ◽  
Caspase 3 ◽  
Stress Proteins ◽  
Protein Hydrolysates ◽  
Cellular Damage ◽  
Enzyme Assays ◽  
Antioxidant Enzyme Activities ◽  
Hepatic Cells ◽  
Oat Bran

The objective of this work was to find out how the method to extract proteins and subsequent enzymatic hydrolysis affect the ability of hepatic cells to resist oxidative stress. Proteins were isolated from oat brans in the presence of Cellulase (CPI) or Viscozyme (VPI). Four protein hydrolysates were produced from CPI and four others from VPI when they treated with Alcalase, Flavourzyme, Papain, or Protamex. Apart from CPI-Papain that reduced the viability of cell by 20%, no other hydrolysate was cytotoxic in the hepatic HepG2 cells. In the cytoprotection test, VPI-Papain and VPI-Flavourzyme fully prevented the damage due to peroxyl radical while CPI-Papain and CPI-Alcalase enhanced the cellular damage. Cells treated with VPI-hydrolysates reduced intracellular reactive oxygen species (ROS) by 20–40% and, also increased the intracellular concentration of glutathione, compared to CPI-hydrolysates. In antioxidant enzyme assays, although all hydrolysates enhanced the activity of both superoxide dismutase and catalase by up to 2- and 3.4-fold, respectively relative the control cells, the largest increase was due to VPI-Papain and VPI-Flavourzyme hydrolysates. In caspase-3 assays, hydrolysates with reduced ROS or enhanced antioxidant enzyme activities were able to reduce the activity of the pro-apoptotic enzyme, caspase-3 indicating that they prevented oxidative stress-induced cell death.

THE ACUTE ORAL TOXICITY OF SPIRAMYCIN

1958 ◽  
Vol 36 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Eldon M. Boyd
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Young Male ◽  
Surface Epithelium ◽  
Albino Rats ◽  
Clinical Effects ◽  
Oral Toxicity ◽  
Hepatic Cells ◽  
Usual Therapeutic Dose ◽  
Tunica Propria

Spiramycin was administered as a suspension by stomach tube in a range of doses to 46 young male albino rats, with 16 controls, and to 14 small mongrel bitches, with eight controls. The oral acute LD50 was found to be 9.4 ± 0.8 g. (mean ± S.D.) per kg. body weight in rats and 5.2 ± 1.6 g. per kg. body weight in dogs. From these values, the oral acute LD50 in man was estimated to be of the order of 1 to 2 g. per kg. body weight or 20 to 40 times the usual therapeutic dose. The clinical effects of these acutely toxic oral doses in rats and dogs were anorexia, vomiting (dogs only), diarrhea, and lassitude, progressing to prostration, pallor, a fall in body temperature, cessation of respiration, and death usually within 48 hours. At autopsy the stomach and intestines were distended with gas and liquid, the tunica propria and submucosa were acutely congested, and there was excessive necrosis and desquamation of the surface epithelium. Areas of acute necrosis were found in the hepatic cells and sinusoids of the liver, and in the (mostly distal) convoluted tubules of the kidney. The cause of death, therefore, was an acute fulminating gastroenteritis accompanied by acute regional necrosis of the liver and kidneys, produced by the orally administered lethal dose of spiramycin.

scholarly journals Distribution of Cytokeratin 17 in the Parenchymal Elements of Rat’s Submandibular Glands Subjected to Fractionated Radiotherapy

2020 ◽  
Vol 14 (03) ◽  
pp. 440-447
Author(s):  
Sherif S. Hassan ◽  
Mahmoud A. Attia ◽  
Alaa M. Attia ◽  
Reda A. Nofal ◽  
Adel Fathi
Keyword(s):  
Submandibular Gland ◽  
Apical Part ◽  
Albino Rats ◽  
Pathological Effect ◽  
Fractionated Radiotherapy ◽  
Cytokeratin 17 ◽  
Neck Malignancy ◽  
Submandibular Salivary Glands ◽  
Mitotic Figures ◽  
Immunohistochemical Studies

Abstract Objectives The aim of this research was to study the intensity of cytokeratin 17 (CK17) in the parenchymal elements of rat’s submandibular salivary glands subjected to fractionated radiotherapy regimen that used for treatment of head and neck malignancy. Materials and Methods Twenty male albino rats were divided into two equal groups (normal and irradiated). The irradiated group received a radiation dose of 5 Grays daily for 5 days using therapeutic X-ray beam. Six months later, submandibular gland was dissected out and prepared for both histological and immunohistochemical studies. Results Submandibular gland of irradiated group showed two different types of histological alterations. The first alteration showed severe gland atrophy replaced by either fibrous or fatty tissues. In some sections, the gland exhibited proliferating activity in the form of profuse amounts of mitotic figures. Immunohistochemical examination of control glands displayed a mild cytoplasmic expression of CK17 of duct cells as well as serous acini. The staining pattern was either diffused or concentrated at the basal part of the cell with negative expression at its apical part. Statistical Analysis Expression of CK17 in submandibular gland of irradiated group displayed a highly significant differences (P < 0.001) in both intercalated and striated ducts. Many serous acini displayed a highly significant differences (P < 0.001) whereas, mucous acini were negatively stained. Conclusions The intensity and diffusion of CK17 expression in our results foretell the pathological effect of radiotherapy on the intermediate filaments of salivary gland parenchyma that interfered with production and/or secretion of saliva leading to xerostomia.

THE LIPOTROPIC ACTION OF COLD: 1. THE INFLUENCE OF COLD AND CHOLINE DEFICIENCY ON LIVER LIPIDS OF RATS AT DIFFERENT INTAKES OF DIETARY METHIONINE

1964 ◽  
Vol 42 (6) ◽  
pp. 769-777 ◽  
Author(s):  
M. W. Radomski ◽  
J. D. Wood
Keyword(s):  
Total Cholesterol ◽  
Cold Exposure ◽  
Free Cholesterol ◽  
Fatty Infiltration ◽  
Albino Rats ◽  
Dietary Intakes ◽  
Choline Deficiency ◽  
Liver Lipids ◽  
Cholesterol Levels

The effect of cold exposure and choline deficiency on the levels of liver lipids of male albino rats was studied at four dietary intakes of methionine (20–100 mg per rat per day). After exposure of the animals to cold (2–3 °C) for a 10-day period, the liver lipids were analyzed for total and free cholesterol, phospholipid, and triglyceride.In choline-fed animals, cold exposure did not affect triglyceride or total cholesterol levels but elevated phospholipid and free cholesterol and decreased ester cholesterol. The increase in phospholipid levels occurred at all methionine intakes with the changes in the cholesterol fractions occurring only at methionine intakes >40 mg per day.In choline-deficient rats, there was evidence that the lipotropic action of cold exposure was related to dietary methionine intake. At methionine intakes <60 mg per rat per day, fatty infiltration of the livers of the choline-deficient cold-exposed rats occurred, as evidenced by the accumulation of triglyceride and ester cholesterol. Concomitantly, phospholipid levels decreased. The data suggest that cold increases the capacity of the animal to synthesize choline from endogenous sources.

scholarly journals RENAL DAMAGE FOLLOWING THE INGESTION OF A DIET CONTAINING AN EXCESS OF INORGANIC PHOSPHATE

1935 ◽  
Vol 61 (3) ◽  
pp. 319-334 ◽  
Author(s):  
Eaton M. MacKay ◽  
Jean Oliver
Keyword(s):  
Inorganic Phosphate ◽  
Potassium Phosphate ◽  
Outer Zone ◽  
Albino Rats ◽  
Renal Lesion ◽  
Atypical Epithelium ◽  
Renal Structure ◽  
Acid Acid ◽  
Outer Stripe ◽  
Convoluted Tubules

The addition of an excess of inorganic phosphate in the form of orthophosphoric acid, acid, basic or neutral sodium or potassium phosphate to the diet of albino rats results in the development of an interesting and permanent renal lesion. The phosphate renal lesion is characterized by a necrosis of the cells of the convoluted tubules commencing at the terminal end, followed by a regeneration of atypical epithelium and calcification of the necrotic debris that fills the tubules. The entire outer stripe of the outer zone of the medulla is transformed into a zone of distorted structures and there is an increase in the interstitial connective tissue. The adjoining cortex is also involved with cystic dilatation of tubules and collapse. Such areas may reach the free surface of the organ and produce a retracted scar. In the gross the kidneys are enlarged and firm on section with a pebbled surface produced by numerous scars. The maximum changes in the kidney structure are reached after some 15 days although necrosis of the convoluted tubule cells is evident after a single day of phosphate feeding. The renal structure is not restored to its normal form when the excess of phosphate is removed from the diet.

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