scholarly journals High-dose testosterone supplementation disturbs liver pro-oxidant/antioxidant balance and function in adolescent male Wistar rats undergoing moderate-intensity endurance training

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10228
Author(s):  
Ewa Sadowska-Krępa ◽  
Barbara Kłapcińska ◽  
Anna Nowara ◽  
Sławomir Jagsz ◽  
Izabela Szołtysek-Bołdys ◽  
...  

In some countries, anabolic-androgenic steroid abuse is rampant among adolescent boys and young men, including some of those seeking physical fitness and/or pleasing appearance through various exercise types. This tactic carries the risk of severe harmful health effects, including liver injury. Most anabolic-androgenic steroid stacking protocols employed are based on the use of the ‘prototypic’ anabolic-androgenic steroid testosterone and/or its esters. There is a vast body of data on the effects of anabolic-androgenic steroids’ abuse combined with physical exercise training on the liver antioxidant barrier in adult subjects, whereas those concerning adolescents are scant. This study aimed to assess, in adolescent male Wistar rats undergoing a 6-week moderate-intensity endurance training (treadmill running), the influence of concurrent weekly supplementation with intramuscular testosterone enanthate (TE, 8 or 80 mg/kg body weight/week) on selected indices of liver status and oxidative stress. The rats were sacrificed, and their livers and blood samples were harvested two days after the last training session. High-dose TE treatment significantly reduced body and liver weight gains. Neither low-dose nor high-dose TE treatment affected liver α-tocopherol or γ-tocopherol content, whereas low-dose TE treatment significantly lowered hepatic reduced glutathione content. TE treatment significantly elevated liver thiobarbituric acid-reactive substances content and blood activities of alkaline phosphatase and γ-glutamyltransferase, but not of aspartate aminotransferase or alanine aminotransferase. Liver catalase activity was lowered by >50% in both TE-treated groups, while superoxide dismutase activity was significantly but slightly affected (−15%) only by the high-dose TE treatment. Glutathione peroxidase and glutathione reductase activities were not significantly altered. TE treatment significantly increased liver thiobarbituric acid-reactive substances content and lowered blood HDL-cholesterol, but did not significantly affect LDL-cholesterol or triglycerides level. In conclusion, high-dose TE treatment significantly disturbed liver antioxidant barrier and prooxidative-antioxidative balance and hence counteracted favorable effects of concurrent moderate-intensity endurance training in adolescent male rats.

2012 ◽  
Vol 124 (3) ◽  
pp. 191-202 ◽  
Author(s):  
Mona Sedeek ◽  
Alex Gutsol ◽  
Augusto C. Montezano ◽  
Dylan Burger ◽  
Aurelie Nguyen Dinh Cat ◽  
...  

Nox (NADPH oxidase)-derived ROS (reactive oxygen species) have been implicated in the development of diabetic nephropathy. Of the Nox isoforms in the kidney, Nox4 is important because of its renal abundance. In the present study, we tested the hypothesis that GKT136901, a Nox1/4 inhibitor, prevents the development of nephropathy in db/db (diabetic) mice. Six groups of male mice (8-week-old) were studied: (i) untreated control db/m, (ii) low-dose GKT136901-treated db/m (30 mg/kg of body weight per day), (iii) high-dose GKT136901-treated db/m (90 mg/kg of body weight per day), (iv) untreated db/db; (v) low dose GKT136901-treated db/db; and (vi) high-dose GKT136901-treated db/db. GKT136901, in chow, was administered for 16 weeks. db/db mice developed diabetes and nephropathy as evidenced by hyperglycaemia, albuminuria and renal injury (mesangial expansion, tubular dystrophy and glomerulosclerosis). GKT136901 treatment had no effect on plasma glucose or BP (blood pressure) in any of the groups. Plasma and urine TBARSs (thiobarbituric acid-reacting substances) levels, markers of systemic and renal oxidative stress, respectively, were increased in diabetic mice. Renal mRNA expression of Nox4, but not of Nox2, increased, Nox1 was barely detectable in db/db. Expression of the antioxidant enzyme SOD-1 (superoxide dismutase 1) decreased in db/db mice. Renal content of fibronectin, pro-collagen, TGFβ (transforming growth factor β) and VCAM-1 (vascular cell adhesion molecule 1) and phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) were augmented in db/db kidneys, with no change in p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). Treatment reduced albuminuria, TBARS and renal ERK1/2 phosphorylation and preserved renal structure in diabetic mice. Our findings suggest a renoprotective effect of the Nox1/4 inhibitor, possibly through reduced oxidative damage and decreased ERK1/2 activation. These phenomena occur independently of improved glucose control, suggesting GKT136901-sensitive targets are involved in complications of diabetes rather than in the disease process.


Author(s):  
Xin Dai ◽  
Xiao-Feng Sun ◽  
Ai-Qin Wang ◽  
Wanhong Wei ◽  
Sheng-Mei Yang

Gallic acid (GA), a phenol that is present in various plants, potentially contains antioxidant properties. This study aimed to investigate the effects of GA on the reproduction of adolescent male Brandt’s voles (Lasiopodomys brandtii (Radde, 1861)). Antioxidant levels and apoptosis in the testis, as well as reproductive physiology, were evaluated in adolescent males treated with GA. The results showed that a low dose of GA enhanced relative epididymis weight and the sperm density in the epididymis, increased the mRNA levels of steroidogenic acute regulatory protein in the testis, and reduced the percentages of abnormal and dead sperm. In addition, a low dose of GA significantly increased the levels of superoxide dismutase, catalase, and glutathione peroxidase, and decreased the level of malondialdehyde in the testis, as well as the mRNA and protein levels of the apoptosis related gene, caspase-3. However, a high dose of GA sharply reduced the average diameter of the seminiferous tubules compared to a low dose. Collectively, these findings demonstrate that GA treatment during puberty affects the reproductive responses of male Brandt’s voles in a dose-dependent manner by regulating antioxidant levels and apoptosis.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3185 ◽  
Author(s):  
Előd Nagy ◽  
Enikő Vajda ◽  
Camil Vari ◽  
Sándor Sipka ◽  
Ana-Maria Fárr ◽  
...  

ObjectiveThis study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.MethodsThirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P,n = 11), low-dose (GrpM Lo, 0.2 mg/kg,n = 12) or high-dose (GrpM Hi, 1 mg/kg,n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.ResultsCompared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 andp = 0.014) and high-dose (p = 0.003 andp = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.ConclusionIn this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.


2018 ◽  
Vol 15 (2) ◽  
pp. 177
Author(s):  
YUNITA SURYA PRATIWI ◽  
SULISTIANA PRABOWO

<p>Administration of high-dose paracetamol may increase metabolic pathways that produce N-acetyl-p-benzoquinonimine (NAPQI). NAPQI is reactive substance, resulting in hepatic tissue damage and increase liver MDA level. Avocado peel extract contains flavonoids that act as antioxidants so it is expected may decrease liver MDA level of high-dose paracetamol administration.</p><p>This research used 24 male Wistar rats divided into 3 groups: group of rats fed with standard food, group of rats given paracetamol 1,750 mg/kg BW on day 8, and group of rats given avocado peel extract 1,400 mg/kg/day for 8 days and paracetamol 1750mg/kg BW on day 8. Liver MDA levels were checked on day 9 by thiobarbituric acid<em> </em>(TBA) method.</p><p>The One-Way ANOVA test showed that the liver MDA level of the group of rats given high dose of paracetamol (=312.38±47.830 nmol/g) was significantly higher (p = 0.001) compared to the liver MDA level of the group of rats fed with standard food (=184.50±57.021 nmol/g). The liver MDA level of group of rats given high-dose paracetamol and avocado peel extract<em> </em>(=268.50±91.834 nmol/g) did not significantly decrease (p =0.213) compared to the liver MDA level of group of rats given high dose of paracetamol (=312.38±47.830 nmol/g).</p><p>The conclusion of this research showed that high-dose paracetamol significantly increased liver MDA level and avocado peel extract tend to decrease liver MDA level because avocado peel consists flavonoid, hydroxynnamic acid<em>, </em>keratinoid, vitamin C, dan vitamin E that function as antioxidants.</p><p> </p><p><strong>Keywords</strong>: <em>Paracetamol, MDA, Persea americana</em></p>


2010 ◽  
Vol 30 (3) ◽  
pp. 199-208 ◽  
Author(s):  
Małgorzata Kujawska ◽  
Ewa Ignatowicz ◽  
Małgorzata Ewertowska ◽  
Jan Oszmiański ◽  
Jadwiga Jodynis-Liebert

Male Wistar rats were treated with chokeberry juice per os, 10 mL/kg/day, for 28 days and a single intraperitoneal (i.p.) dose of N-nitrosodiethylamine (NDEA), 150 mg/kg, or carbon tetrachloride (CCl4), 2 ml/kg. The level of hepatic microsomal lipid peroxidation, expressed as thiobarbituric acid reactive substances (TBARS), was increased in animals dosed with NDEA and CCl4. Juice pretreatment resulted in a significant decrease in TBARS by 53% and 92%, respectively. In rats administered juice alone, 50% decrease in TBARS was noted. The activities of all antioxidant enzymes were decreased in the liver of rats administered either toxicant by 29%—52% as compared to controls. Juice pretreatment resulted in an increase in the activity of catalase, glutathione peroxidase and glutathione reductase by 117%, 56% and 44%, respectively, only in rats challenged with NDEA. Although no response of plasma protein carbonyls to both toxicants was observed, the pretreatment with juice caused a 55% decrease of this parameter in CCl4—dosed rats. DNA damage in blood leukocytes induced by either toxicant was slightly reduced, by 24%, in the rats pretreated with juice and administered NDEA. The results of the study showed that pretreatment with chokeberry juice confers some protection against chemical-induced oxidative stress.


2003 ◽  
Vol 89 (1) ◽  
pp. 89-96 ◽  
Author(s):  
S. L. de Oliveira ◽  
D. B. Diniz ◽  
J. Amaya-Farfan

Chronic energy restriction, α-tocopherol supplementation and their interaction with exhaustive exercise were investigated. Eleven-week-old male Wistar rats (n 6×10) were fed either a control (C), a 30 % carbohydrate-energy-restricted control (R) or an α-tocopherol-supplemented (S) diet for 5 months. The animals in each diet were divided into exercised (E) and non-exercised (NE) groups. Before killing, the exercised rats were required to run to exhaustion (39 (SE 6), 69 (se 11) and 18 (se 2) min for the C, R and S groups, respectively). Lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), protein damage (reactive carbonyls) and α-tocopherol were determined in gastrocnemius, liver, brain an/r plasma. There was no difference in lipid peroxidation between the R and C groups, but in liver and muscle peroxidation appeared significantly lower in the S than the other two diets. TBARS in the brain were similar in all groups. On the other hand, reactive carbonyls showed that both the R and S diets reduced protein damage in the brain, while exhaustive exercise increased it. For liver and muscle, however, reactive carbonyl levels were similar in all groups. α-Tocopherol supplementation increased the vitamin concentrations in liver, muscle and plasma, but exercise decreased them in plasma and brain. Carbohydrate-energy restriction increased (P=0·0025) resistance to exhaustive exercise considerably without depleting stores of α-tocopherol or exacerbating oxidative damage in monitored tissues. It is concluded that while exhaustive exercise promotes a tissue-specific oxidative damage detectable only in brain proteins, both experimental diets tended to ameliorate this condition.


2011 ◽  
Vol 11 (2) ◽  
pp. 118-127 ◽  
Author(s):  
Ewa Sadowska-Krępa ◽  
Barbara Kłapcińska ◽  
Sławomir Jagsz ◽  
Andrzej Sobczak ◽  
Stanisław J. Chrapusta ◽  
...  

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