Comparative effect of indomethacin (IndoM) on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in the kidney, small intestine and liver of rats

Autor: Sheeba Khan, Ahad N.K. Yusufi, Faiz Noor Khan Yusufi
Rok vydání: 2018
Předmět:
G6PDH
Glucose-6-phosphate dehydrogenase an enzyme
Health
Toxicology and Mutagenesis
Indomethacin
ALP
Alkaline phosphatase an enzyme
010501 environmental sciences
Toxicology
medicine.disease_cause
Kidney
01 natural sciences
Lipid peroxidation
chemistry.chemical_compound
0302 clinical medicine
TCA cycle
Tri-carboxylic acid cycle
GGTase
γ-Glutammyl transferase an enzyme
BBMV
Brush border membrane vesicles
Pi
Inorganic phosphate
Chemistry
ME
Malic enzyme an enzyme
ACPase
Acid phosphatase an enzyme
LAP
Leucine amino peptidase
an enzyme
Intestine
medicine.anatomical_structure
ATP
Adenosine 5’-triphosphate energy currency
BUN
Blood urea nitrogen blood parameter
Liver
Toxicity
Alkaline phosphatase
SH
Sulfhydryl groups
ANOVA
Analysis of variance statistical tool
medicine.medical_specialty
NADP+
Nicotinamide adenine dinucleotide phosphate
MDH
Malate dehydrogenase an enzyme
Carbohydrate metabolism
Article
NADPH
Nicotinamide adenine dinucleotide phosphate (reduced) reducing equivalent
03 medical and health sciences
BBM
Brush border membrane intestinal membrane
lcsh:RA1190-1270
LPO
Lipid peroxidation
Internal medicine
Lactate dehydrogenase
medicine
G6Pase
Glucose-6-phosphatase an enzyme
lcsh:Toxicology. Poisons
0105 earth and related environmental sciences
LDH
Lactate dehydrogenase an enzyme
Metabolism
Small intestine
Endocrinology
HMP
Hexose monophosphate
SOD
Superoxide dismutase
an enzyme
Anaerobic glycolysis
Oxidative stress
HK
Hexokinase an enzyme
030217 neurology & neurosurgery
ROS
Reactive oxygen species
Zdroj: Toxicology Reports
Toxicology Reports, Vol 6, Iss, Pp 389-394 (2019)
ISSN: 2214-7500
Popis: Highlights • Indomethacin (IndoM) administration causes renal, hepatic and intestinal toxicity. • The renal proximal tubule, intestinal mucosa particularly their BBM and liver seem to be the major IndoM targets. • IndoM produces multiple adverse effects in the liver, kidney, and intestine and alters metabolic functions. • IndoM shifts energy dependence from oxidative metabolism to anaerobic glycolysis by causing damage to mitochondria. • IndoM caused nephrotoxicity and other effects by increasing ROS generation and suppression of antioxidant mechanism.
Indomethacin (IndoM) has prominent anti-inflammatory and analgesic-antipyretic properties. However, high incidence and severity of side-effects on the structure and functions of the kidney, liver and intestine limits its clinical use. The present study tested the hypothesis that IndoM causes multi-organ toxicity by inducing oxidative stress that alters the structure of various cellular membranes, metabolism and hence functions. The effect of IndoM was determined on the enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in the rat kideny, liver and intestine to understand the mechanism of IndoM induced toxicity. Adult male Wister rats were given IndoM (20 mg/kg) intra-peritoneally in sodium bicarbonate twice a day for 3 d. The body weights of the rats were recorded before and after experimental procedure. IndoM administration significantly increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but inorganic phosphate indicating IndoM induced renal, hepatic and intestinal toxicity. Activity of lactate dehydrogenase along with glucose-6- and fructose-1, 6-bis phosphatase, glucose-6-phosphate dehydrogenase and NADP-malic enzyme increased but malate dehydrogenase decreased in all tissues. Lipid peroxidation (LPO) significantly increased whereas the antioxidant enzymes decreased in all rat tissues studied. The results indicate that IndoM administration caused severe damage to kidney, liver and intestine by icreasing LPO, suppressing antioxidant enzymes and inhibiting oxidative metablolism. The energy dependence was shifted to anaerobic glycolysis due to mitochondrial damage supported by increased gluconeogenesis to provide more glucose to meet energy requirements.
Databáze: OpenAIRE
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