Drug-induced morphological alterations in liver

1993 ◽  
Vol 51 ◽  
pp. 390-391
Author(s):  
Moustafa Mohamad ◽  
Richard L. Drake ◽  
Robert R. Cardell
Keyword(s):  
Smooth Endoplasmic Reticulum ◽  
Anticonvulsant Drug ◽  
Chronic Administration ◽  
Male Rats ◽  
Hepatic Glycogen ◽  
Drug Induced ◽  
Hepatocyte Ultrastructure ◽  
Morphological Alterations ◽  
Treatment Groups ◽  
Antituberculous Drug

Chronic administration of phenobarbital, an anticonvulsant drug, or rifampicin, an antituberculous drug, alters hepatocyte ultrastructure by inducing the proliferation of smooth endoplasmic reticulum (SER) and changes in glycogen content. While these generalized effects are important, the lobular location of hepatocytes must be considered since pericentral and periportal hepatocytes differ morphologically and most hepatotoxic compounds affect specific zones of the liver. We treated adult male rats with phenobarbital or rifampicin for 5 days to evaluate the effect of each drug on hepatic glycogen levels, glycogen distribution across the liver lobule, and hepatocyte ultrastructure, especially the SER. Our results show a decrease in hepatic glycogen levels as determined biochemically in both treatment groups. Semithin sections of liver specifically stained for glycogen (Figs. 1-3) show that in treated animals glycogen in pericentral and periportal hepatocytes is reduced (Figs. 2,3). Ultrastructurally, periportal hepatocytes typically have clumped glycogen (Fig. 4); however, in treated animals periportal hepatocytes that show the greatest reduction of glycogen contain extensive SER (Fig. 5).

Multigeneration Reproduction Study of Lactitol in Rats

1992 ◽  
Vol 11 (2) ◽  
pp. 233-248 ◽  
Author(s):  
E.J. Sinkeldam ◽  
V.M.H. Hollanders ◽  
R.A. Woutersen ◽  
H.B.W.M. Koëter ◽  
A. Bär
Keyword(s):  
Adverse Effects ◽  
Reproductive Performance ◽  
Histopathological Examination ◽  
Chronic Administration ◽  
Female Rats ◽  
Morphological Alterations ◽  
Treatment Groups ◽  
Reproduction Study ◽  
Successive Generations ◽  
Similar Growth

Lactitol is a disaccharide sugar alcohol (polyol) which holds promise as a reduced calorie, noncariogenic sugar substitute. In a multigeneration reproduction study, lactitol was fed to Wistar-derived Cpb:WU rats of both sexes throughout three successive generations at dietary concentrations of 0, 2, 5, and 10%. A comparison group receiving a diet with 20% lactose was included during the F., generation. The initial mating comprised 20 male and 40 female rats per group. For subsequent matings, 10 males and 20 females were used. In each generation, two litters were reared until they were at least 3 weeks old. Fertility was uniformly high in all treatment groups throughout the study and the feeding of lactitol was not associated with any adverse effects on fertility and reproductive performance. However, growth rates and survival were slightly decreased in pups of the 10% lactitol group, except in F3 litters where no effect of lactitol on survival was seen. In the 20% lactose group of the F, generation, a similar growth retardation and decreased survival was seen. The second litter of third-generation rats (F3b) was subjected to gross and histopathological examination 4 weeks after weaning. F3b rats fed 5 or 10% lactitol showed cecal enlargement which was not associated with any morphological alterations and which is commonly seen in rodents fed polyols or slowly digestible carbohydrates. In some F3b males of all dosage groups, an opaque appearance of the liver cell cytoplasm was noted. However, this effect was not dose related and was not accompanied by any other hepatic changes in the lactitol groups. Since this phenomenon was not seen in older rats or after chronic administration of lactitol, it was considered to be a transient manifestation of an altered metabolism in young rats. All other histopathological findings were equally distributed between control and test animals, or occurred in one or a few rats only. It is concluded that lactitol administered in the diet to three successive generations of rats at levels up to 10%, has no adverse effects on reproductive performance in either sex. The slight developmental delay which occurred in some generations, has been observed earlier with other polyols and may be attributed to the poor digestibility of these compounds.

Morphological and biochemical analyses of changes in rat hepatocytes related to wine and ethanol consumption

1984 ◽  
Vol 42 ◽  
pp. 232-233
Author(s):  
S.M. Geyer ◽  
C.L. Mendenhall ◽  
J.T. Hung ◽  
E.L. Cardell ◽  
R.L. Drake ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Malic Enzyme ◽  
Smooth Endoplasmic Reticulum ◽  
Rat Hepatocytes ◽  
Mature Male ◽  
Treatment Groups ◽  
Malic Enzyme Activity ◽  
Biochemical Analyses

Thirty-three mature male Holtzman rats were randomly placed in 3 treatment groups: Controls (C); Ethanolics (E); and Wine drinkers (W). The animals were fed synthetic diets (Lieber type) with ethanol or wine substituted isocalorically for carbohydrates in the diet of E and W groups, respectively. W received a volume of wine which provided the same gram quantity of alcohol consumed by E. The animals were sacrificed by decapitation after 6 weeks and the livers processed for quantitative triglycerides (T3), proteins, malic enzyme activity (MEA), light microscopy (LM) and electron microscopy (EM). Morphometric analysis of randomly selected LM and EM micrographs was performed to determine organellar changes in centrilobular (CV) and periportal (PV) regions of the liver. This analysis (Table 1) showed that hepatocytes from E were larger than those in C and W groups. Smooth endoplasmic reticulum decreased in E and increased in W compared to C values.

DER EINFLUSS VON RESERPIN AUF DIE ANTITHYREOIDALE WIRKUNG VON KALIUMPERCHLORAT

1962 ◽  
Vol 39 (3) ◽  
pp. 423-430
Author(s):  
H. L. Krüskemper ◽  
F. J. Kessler ◽  
E. Steinkrüger
Keyword(s):  
Thyroid Gland ◽  
Male Rats ◽  
Normal Male ◽  
Tissue Respiration ◽  
List Type ◽  
Morphological Alterations ◽  
Hormone Synthesis ◽  
Stimulation Of

ABSTRACT 1. Reserpine does not inhibit the tissue respiration of liver in normal male rats (in vitro). 2. The decrease of tissue respiration of the liver with simultaneous morphological stimulation of the thyroid gland after long administration of reserpine is due to a minute inhibition of the hormone synthesis in the thyroid gland. 3. The morphological alterations of the thyroid in experimental hypothyroidism due to perchlorate can not be prevented with reserpine.

Dobutamine as a countermeasure for reduced exercise performance of rats exposed to simulated microgravity

1997 ◽  
Vol 82 (5) ◽  
pp. 1607-1615 ◽  
Author(s):  
Charles M. Tipton ◽  
Lisa A. Sebastian
Keyword(s):  
Lactic Acid ◽  
Exercise Performance ◽  
Simulated Microgravity ◽  
Maximal Exercise ◽  
Blood Gases ◽  
Chronic Administration ◽  
Mechanical Efficiency ◽  
Male Rats ◽  
Double Product ◽  
Run Time

Tipton, Charles M., and Lisa A. Sebastian. Dobutamine as a countermeasure for reduced exercise performance of rats exposed to simulated microgravity. J. Appl. Physiol. 82(5): 1607–1615, 1997.—Post-spaceflight results and findings from humans and rodents after conditions of bed rest or simulated microgravity indicate maximum exercise performance is significantly compromised. However, the chronic administration of dobutamine (a synthetic adrenomimetic) to humans in relevant experiments improves exercise performance by mechanisms that prevent the decline in peak O2 consumption (V˙o 2 peak) and reduce the concentration of lactic acid measured in the blood. Although dobutamine restores maximumV˙o 2values in animals participating in simulated microgravity studies, it is unknown whether injections of this α1-, β1-, and β2-adrenoceptor agonist in rats will enhance exercise performance. To investigate this, adult male rats were assigned to three experimental groups: caged control receiving saline; head-down, tail-suspended (HDS) receiving saline (HDS-S); and an HDS group receiving dobutamine hydrochloride injections (1.8 mg/kg twice daily per rat). Treadmill tests were performed before suspension, at 14 days, and after 21 days.V˙o 2 peak, run time, and the rate of rise in colonic temperature (heating index) were evaluated after 14 days, whereas at 21 days, hemodynamic responses (heart rate, systolic blood pressure, and double product) were determined during submaximal exercise with blood pH, blood gases, and lactic acid concentration values obtained during maximal exercise. In contrast to the results for the HDS-S rats, dobutamine administration did restore V˙o 2 peakand “normalized” lactic acid concentrations during maximal exercise. However, daily injections were unable to enhance exercise performance aspects associated with treadmill run time, the mechanical efficiency of running, the heating index, or the retention of muscle and body mass. These simulated microgravity findings suggest that dobutamine’s potential value as a countermeasure for postflight maximal performance or for egress emergencies is limited and that other countermeasures must be considered.

Testosterone Depletion and Its Possible Mechanism of Action by Chronic Administration of Metastin Analogs, KiSS1-305, TAK-448, and TAK-683, in Adult Male Rats

2011 ◽  
pp. P3-148-P3-148
Author(s):  
Hisanori Matsui ◽  
Akira Tanaka ◽  
Kotaro Yokoyama ◽  
Yoshihiro Takatsu ◽  
Kaori Ishikawa ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Adult Male ◽  
Chronic Administration ◽  
Male Rats

scholarly journals Effect of Administration of Combination of Captopril and Celery Extract on Blood Pressure and Electrolyte Levels of Hypertensive Rats

2020 ◽  
Vol 7 (3) ◽  
pp. 81
Author(s):  
Siska Siska ◽  
Franciscus D. Suyatna ◽  
Abdul Mun'im ◽  
Anton Bahtiar
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Concomitant Administration ◽  
Reduce Blood Pressure ◽  
Male Rats ◽  
Apium Graveolens ◽  
Hypertensive Rats ◽  
Treatment Groups ◽  
Urinary Potassium ◽  
Standard Value

Based on previous reports, the combination of captopril and celery could reduce blood pressure in hypertensive patients. This study aimed to investigate the changes of blood pressure, urine volume, sodium, and potassium level, due to concomitant administration of captopril with celery extract orally in male rats induced by 4% NaCl. The blood pressure was measured using a non-invasive tail method. The urine and blood were collected, and the sodium, potassium concentration, and cumulative urine volume were measured. The combination of 5 mg/kgBW of captopril and 40 mg/kgBW of celery extract decreased the blood pressure in hypertensive rats better than 5 mg/kgBW of captopril alone. The fell in blood pressure was followed by an increase in urine volume. Urinary and serum sodium, serum potassium levels tended to increase in all treatment groups, but not significantly different from the healthy group. Urinary potassium levels tended to decrease except in the combined 5 mg/kgBW of captopril and 40 mg/kgBW of celery extract. In conclusion, oral administration of a combination of 5 mg/kgBW captopril and 40 mg/kgBW celery extract decreased the blood pressure to the standard value in NaCl-induced hypertension rats.Keywords: Apium graveolens, captopril, celery, hypertension, pharmacodynamic

scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

2021 ◽  
Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Chronic Administration ◽  
Stress Factors ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Organic Nitrates ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

DRUG INTERACTIONS—PART III

PEDIATRICS ◽  
1972 ◽  
Vol 50 (3) ◽  
pp. 489-490
Author(s):  
Lester F. Soyka
Keyword(s):  
Enzyme Induction ◽  
Specific Activity ◽  
Smooth Endoplasmic Reticulum ◽  
Chronic Administration ◽  
Concurrent Administration ◽  
Protein Mass ◽  
Carcinogenic Potential ◽  
Activity Of Enzymes ◽  
Practice Activity ◽  
Cellular Components

ENZYME induction is defined as an increase in the specific activity of enzymes which metabolize foreign substances (e.g., drugs, chemicals, and insecticides) and certain endogenous compounds (e.g., steroids and fatty acids). In practice, activity, rather than actual enzyme protein mass relative to structural cellular components, is usually determined. Most of the drug-metabolizing (microsomal) enzymes are in the liver; however, lesser activity is found in the skin, placenta, kidney, lung, etc., and induction in these organs has been demonstrated. In 1956 Conney et al.1 observed that chronic administration of 3-methylcholanthrene (3-MC) caused an increase in its own rate of metabolism, thereby decreasing its carcinogenic potential. Remmer and Merker2 found that the tolerance of animals to chronic barbiturate administration was partly due to an increased rate of metabolic inactivation, and that hypertrophy of the smooth endoplasmic reticulum of hepatocytes resulted from such treatment. Subsequent investigations have shown that more than 200 drugs and chemicals cause enzyme induction in animals3 and several of these are known to be active in man. Inducers are of three types: small organic molecules, e.g., phenobarbital; chlorinated hydrocarbons, e.g., DDT; and polycydic hydrocarbons, e.g., the environmental polycyclic carcinogens 3-MC and 3,4 benzpyrene. Many clinical reports indicate that important modifications of a drug's effectiveness and safety may arise through induction during continued administration, or through concurrent administration of other drugs. These modifications are: (1) a decrease in effectiveness from acceleration of the rate of inactivation and excretion, (2) an increase in effectiveness from an increase in the rate of biotransformation to an active metabolite, or (3) either of these arising from the action of a previously or concurrently administered inducing drug.

Anticonvulsant-Drug-Induced Mineral Disorders

2020 ◽  
pp. 409-427
Author(s):  
Theodore J. Hahn ◽  
Louis V. Avioli
Keyword(s):  
Anticonvulsant Drug ◽  
Drug Induced
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