Repeated acetaminophen dosing in rats: adaptation of hepatic antioxidant system

2000 ◽  
Vol 19 (5) ◽  
pp. 277-283 ◽  
Author(s):  
P J O'Brien ◽  
M R Slaughter ◽  
A Swain ◽  
J M Birmingham ◽  
R W Greenhill ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant System ◽  
Total Antioxidant Status ◽  
Male Rats ◽  
Glutathione Depletion ◽  
Sprague Dawley ◽  
Hepatocellular Injury ◽  
Total Antioxidant ◽  
Repeated Dosing ◽  
Antioxidant Markers

Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease their sensitivity to its hepatotoxic effects, which are associated with oxidative stress and glutathione depletion. We determined if repeated acetaminophen dosing produced adaptive response of key antioxidant system enzymes. Male rats (Sprague-Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral gavage for 4 days. Liver was assayed for oxidative stress and antioxidant markers: malondialdehyde (MDA), thiobar-bituric acid reactive substance (TBARS), total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker of hepatocellular injury. Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%, GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91; SOD, r=0.66; GPx, r = 0.45). Despite antioxidant deficiencies, and no TBARS change, MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased GR (61%/62%/76%, r = 0.77) and G6PD (130%/110%/190%, r = 0.78). Both MDA (r = 0.68) and G6PD (r = 0.71) correlated with hepatic ALT, which decreased 27%o/43%/48%, respectively. Resistance to acetaminophen hepatotoxicity produced by repeated exposure is partially attributable to upregulation of hepatic G6PD and GR activity as an adaptive and protective response to oxidative stress and glutathione depletion.

scholarly journals Are insulin-resistance and oxidative stress cause or consequence of aging

2020 ◽  
Vol 245 (14) ◽  
pp. 1260-1267
Author(s):  
Sylwia Dzięgielewska-Gęsiak ◽  
Dorota Stołtny ◽  
Alicja Brożek ◽  
Małgorzata Muc-Wierzgoń ◽  
Ewa Wysocka
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Antioxidant Status ◽  
Antioxidant Defense ◽  
Total Antioxidant Status ◽  
Thiobarbituric Acid ◽  
Elderly Individuals ◽  
Total Antioxidant ◽  
Antioxidant Defense Systems ◽  
Antioxidant Markers

Insulin resistance (IR) may be associated with oxidative stress and leads to cardiovascular disorders. Current research focuses on interplay between insulin-resistance indices and oxidant-antioxidant markers in elderly individuals with or without insulin-resistance. The assessment involved anthropometric data (weight, height, BMI, percentage of body fat (FAT)) and biochemical tests (glucose, lipids, serum insulin and plasma oxidant-antioxidant markers: Thiobarbituric Acid-Reacting Substances (TBARS), Cu,Zn-superoxide dismutase (SOD-1) and total antioxidant status). Insulin resistance index (IR) assuming a cut-off point of 0.3 allows to divides groups into: insulin sensitive group (InsS) IR < 0,3 ( n = 35, median age 69.0 years) and insulin-resistant group (InsR) IR ≥ 0.3 ( n = 51, median age 71.0 years). Lipids and antioxidant defense system markers did not differentiate the investigated groups. In the InsR elderly group, the FAT was increased ( P < 0.000003) and TBARS ( P = 0.008) concentration decreased in comparison with InsS group. A positive correlation for SOD-1 and total antioxidant status ( P < 0.05; r =  0.434) and a negative correlation for TBARS and age ( P < 0.05 with r = −0.421) were calculated in InsR individuals. In elderly individuals, oxidative stress persists irrespective of insulin-resistance status. We suggest that increased oxidative stress may be consequence of old age. An insulin action identifies those at high risk for atherosclerosis, via congruent associations with oxidative stress and extra- and intra-cellular antioxidant defense systems. Thus, we maintain that insulin-resistance is not the cause of aging. Impact statement Insulin resistance is associated with oxidative stress leading to cardiovascular diseases. However, little research has been performed examining elderly individuals with or without insulin-resistance. We demonstrate that antioxidant defense systems alone is not able to abrogate insulin action in elderly individuals at high risk for atherosclerosis, whereas the combined oxidant-antioxidant markers (thiobarbituric acid-reacting substances (TBARS), Cu,Zn-superoxide dismutase (SOD-1), and total antioxidant status (TAS)) might be more efficient and perhaps produce better clinical outcome. In fact, a decrease in oxidative stress and strong interaction between antioxidant defense can be seen only among insulin-resistant elderly individuals. This is, in our opinion, valuable information for clinicians, since insulin-resistance is considered strong cardiovascular risk factor.

scholarly journals Effects of Acute Administration of D,L-Homocysteine Thiolactone on the Antioxidative Status of Rat Intestine and Liver

2016 ◽  
Vol 66 (1) ◽  
pp. 26-36 ◽  
Author(s):  
Marija Stojanović ◽  
Ljiljana Šćepanović ◽  
Olivera Bosnić ◽  
Dušan Mitrović ◽  
Olga Jozanov-Stankov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Defense Mechanism ◽  
Total Antioxidant Status ◽  
Male Rats ◽  
Control Group ◽  
Acute Administration ◽  
Rat Intestine ◽  
Homocysteine Thiolactone ◽  
Total Antioxidant

AbstractOxidative stress appears to play a role in the pathogenesis of several inflammatory gastrointestinal diseases. Increased homocysteine levels may play a role in the pathogenesis of Chron’s disease and ulcerative colitis. The aim of this study was to examine the influence of homocysteine on the antioxidant status of rat intestine and liver. The levels of thiobarbituric acid reactive substances (TBARS), activity of catalase (CAT) and total antioxidant status (TAS) were investigated in the isolated gut and liver of young male rats in the control group (8 rats) and after 3-hоur incubation in high doses of D, L-homocysteine thionolactone (Hcy) (10 μmol/L) (8 rats). Samples of duodenum, ileum, colon and liver were homogenized in sodium phosphate buffer (1:10). Homogenates were centrifuged at 10000 for 10 min at 4° C and the supernatant was taken for biochemical assays. Our results showed that high D, L-homocysteine thionolactone concentration reduced enzymatic catalase activity in homogenates of the isolated segments of duodenum (27.04%) p<0.01; ileum (37.27%), colon (34.17%) and liver (67.46%) p<0.001. Exposition to high D,L-homocysteine thiolactone concentration significantly increased TBARS levels in the duodenum (106.05%), ileum (47.24%), colon (112.75%) and liver (32.07%) (p<0.01). Homocysteine also modifi ed the total antioxidant status of homogenates from the duodenum, ileum, colon and liver, increasing by 20.68% (duodenum), 24.74% (ileum), 14.88% (colon) and 19.35% (liver) (p<0.001). Homocysteine induced a consistent oxidative stress in rat’s intestine and liver (reduced activity of catalase and increased level of TBARS), but the elevated activity of TAS in our experiments could be explained as an adaptive response to the generated free radicals which indicates the failure of the total antioxidant defense mechanism to protect the tissues from damage caused by homocysteine.

scholarly journals Occurrence of oxidative stress in sheep during different pregnancy periods

2021 ◽  
Vol 26 (52) ◽  
pp. 111-116
Author(s):  
Tamer Tashla ◽  
Milivoje Ćosić ◽  
Vladimir Kurćubić ◽  
Radivoj Prodanović ◽  
Nikola Puvača
Keyword(s):  
Oxidative Stress ◽  
Total Antioxidant Status ◽  
Late Pregnancy ◽  
Economic Losses ◽  
Productive Performance ◽  
Pregnant Sheep ◽  
Total Antioxidant ◽  
Antioxidant Markers ◽  
Oxidant Status ◽  
Late Stages

The objective of this paper was to evaluate oxidative stress during different pregnancy stages in Lohi sheep reared in Libya. Investigations were carried out on Lohi sheep between 1.5 and 5 years of age. A total of 40 sheep were sub-grouped into various stages of pregnancy along with non-pregnant controls as follows: non-pregnant (n=10), early pregnancy (n=10), mid pregnancy (n=10), and late pregnancy (n=10). Blood samples were collected from pregnant sheep and preserved at -20°C and further used for evaluating the concentrations of total antioxidant status (TAS), total oxidant status (TOS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and paraoxonase (PON-1). In pregnant sheep, TAS, TOS, MDA, SOD, CAT, and PON-1 values were significantly (P < 0.05) different. TOS and MDA increased from non-pregnant ewes to early, mid and late stages of pregnancy whereas TAS, SOD, CAT, and PON-1 significantly (P < 0.05) decreased with the progression of pregnancy. The study suggests that the use of oxidant and antioxidant markers along with the blood metabolic profile should be the recommended procedure for monitoring health status during pregnancy to evade reduced productive performance and economic losses.

scholarly journals The preventive role of Spirulina platensis (Arthrospira platensis) in immune and oxidative insults in a stress-induced rat model

2021 ◽  
Vol 65 (2) ◽  
pp. 193-200
Author(s):  
Nilay Seyidoğlu ◽  
Eda Köşeli ◽  
Rovshan Gurbanlı ◽  
Cenk Aydın
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Rat Model ◽  
Spirulina Platensis ◽  
Arthrospira Platensis ◽  
Male Rats ◽  
Sprague Dawley ◽  
Immunological Parameters ◽  
Serum Corticosterone ◽  
Total Antioxidant

Abstract Introduction There is a balance between oxidative stress, antioxidant capacity and immune response. Their roles in physiological and behavioural mechanisms are important for the maintenance of the organism’s internal equilibrium. This study aimed to evaluate the antioxidant effects of the exogenous alga Spirulina platensis (Arthrospira platensis) in a stress-induced rat model, and to describe its possible mechanism of action. Material and Methods Thirty-six adult male Sprague Dawley rats were separated into four groups: control (C), stress (S), S. platensis (Sp), and S. platensis + stress (SpS). The rats in groups Sp and SpS were fed with 1,500 mg/kg b.w./day Spirulina platensis for 28 days. All rats were exposed to prolonged light phase conditions (18 h light : 6 h dark) for 14 days. The SpS and S groups were exposed to stress by being kept isolated and in a crowded environment. Blood samples were obtained by puncturing the heart on the 28th day. The effect of stress on serum corticosterone, oxidative stress markers (TOS, TAC, PON1, OSI) and immunological parameters (IL-2, IL-4, IFN-ɣ) were tested. Also, the brain, heart, intestines (duodenum, ileum, and colon), kidney, liver, spleen, and stomach of the rats were weighed. Results Serum corticosterone levels were higher in the S group than in the C group, and significantly lower in the SpS group than in the S group. Mean total antioxidant capacity were lower in the S group than in the C group, and Spirulina reversed this change. Although not significantly different, IL-2 was lower in the S group than in the C group. However, in the SpS group, IL-2 increased due to Spirulina platensis mitigating effects of stress. Conclusion Male rats fed a diet with Spirulina platensis could experience significantly milder physiological changes during stress, although stress patterns may be different. Exogenous antioxidant supplements merit further investigation in animals and humans where the endogenous defence mechanism against stress may not be sufficient.

Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis

2020 ◽  
pp. 1-8
Author(s):  
Hasan Haci Yeter ◽  
Berfu Korucu ◽  
Elif Burcu Bali ◽  
Ulver Derici
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Antioxidant Status ◽  
Total Antioxidant Status ◽  
Stress Index ◽  
Total Oxidant Status ◽  
Vitamin D Analog ◽  
Total Antioxidant ◽  
Oxidant Status ◽  
And Oxidative Stress

Abstract. Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

scholarly journals Assessment of oxidative stress in saliva of children with dental erosion

2018 ◽  
Vol 16 (2) ◽  
Author(s):  
Caleb Shitsuka ◽  
Flávia Kazue Ibuki ◽  
Fernando Neves Nogueira ◽  
Fausto Medeiros Mendes ◽  
Marcelo Bönecker
Keyword(s):  
Oxidative Stress ◽  
Erosive Wear ◽  
Total Antioxidant Status ◽  
Pediatric Dentistry ◽  
Dental Erosion ◽  
Dental Biofilm ◽  
Total Antioxidant ◽  
Unstimulated Saliva ◽  
Biochemical Analyses ◽  
Saliva Flow

ABSTRACT Objective To evaluate oxidative stress in saliva of children with dental erosion as compared to children with no erosion. Methods One single examiner, trained and prepared to make diagnosis of dental erosion according to the Basic Erosive Wear Examination index, selected 40 children aged 4 to 6 years, who attended a pediatric dentistry prevention clinic. Two groups were formed - one comprising children with dental erosion (n=22), and another with no dental erosion (n=18). The quantity of dental biofilm was verified using the Simplified Index of Oral Hygiene, and unstimulated saliva was collected for biochemical analyses. The following were assessed in saliva: flow rate, buffering capacity, pH, and total protein concentration. Malondialdehyde levels were also verified to determine oxidative stress and total antioxidant status. Results The quantity of biofilm was smaller in children with mean dental erosion±standard deviation (0.76±0.25), as compared to those with no dental erosion (1.18±0.28). There was no statistical difference in saliva parameters of oxidative stress in children with dental erosion. Conclusion The activity of oxidative stress in saliva did not influence dental erosion process when in its early stages.

scholarly journals TUALANG HONEY ATTENUATES KAINIC ACID-INDUCED OXIDATIVE STRESS IN RAT CEREBELLUM AND BRAINSTEM

2017 ◽  
Vol 9 (12) ◽  
pp. 155 ◽  
Author(s):  
Nur Shafika Mohd Sairazi ◽  
K. N. S. Sirajudeen ◽  
Mustapha Muzaimi ◽  
Mummedy Swamy ◽  
Mohd Asnizam Asari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Total Antioxidant Status ◽  
Thiobarbituric Acid ◽  
Protein Carbonyl ◽  
Multiple Time ◽  
Rat Cerebellum ◽  
Total Antioxidant ◽  
Multiple Time Points ◽  
Tualang Honey

Objective: The present study examined the protective effect of tualang honey (TH) against kainic acid (KA)-induced oxidative stress in the cerebellum and brainstem of rats.Methods: Male Sprague-Dawley rats were randomly divided into four groups: Control, KA-treated, TH+KA-treated, and topiramate (TPM, an antiepileptic agent)+KA-treated groups. Rats were pretreated orally with drinking water, TH (1.0 g/kg body weight), or TPM (40 mg/kg body weight), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Oxidative stress markers were analyzed in different brain regions (cerebellum and brainstem) 2 h, 24 h, and 48 h after KA administration.Results: KA caused significant (p<0.05) elevation in the thiobarbituric acid reactive substances level, protein carbonyl contents, and nitric oxide production, impairment of glutathione system, and a significant reduction in the total antioxidant status in the rat cerebellum and brainstem at multiple time-points, as compared to control groups. Pretreatment with TH significantly (p<0.05) reduced the elevation in the thiobarbituric acid reactive substances level, protein carbonyl contents, and nitric oxide production and increasing a reduction in the total antioxidant status in the rat cerebellum and brainstem induced by KA at multiple time-points, as compared to KA only-treated group.Conclusion: Taken together, this study suggests that TH has therapeutic potential in reducing oxidative stress in the cerebellum and brainstem of KA-induced rats via its antioxidant property.

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