scholarly journals The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver

2021 ◽  
Vol 22 (3) ◽  
pp. 1242
Author(s):  
Paulina Kur ◽  
Agnieszka Kolasa-Wołosiuk ◽  
Marta Grabowska ◽  
Andrzej Kram ◽  
Maciej Tarnowski ◽  
...  

Background: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5α-reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T–DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. Methods: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman’s rank correlation coefficients. Results: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). Conclusions: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis.

1970 ◽  
Vol 36 (1) ◽  
pp. 103-109 ◽  
Author(s):  
S Talukder ◽  
MA Hossain ◽  
S Sarker ◽  
MAH Khan

To evaluate the antifertility effect of crude mixture of A. precatorius seeds at the dose level of 50 mg/kg body weight in adult male rats, after oral administration to male rats for 40 days, the rats were sacrificed and hormonal profiles, serum biochemistry, sperm count and histological changes were recorded. A sharp decrease in the serum levels of testosterone (0.70 ± 0.17 ng/ml), FSH (0.70 ± 0.22 lU/L), and LH (0.87 ± 0.35 IU/L) was detected compared to control (FSH, LH and testosterone levels 0.93 ± 0.15 ng/ml, 0.76 ± 0.28 IU/L, 1.44 ± .011 IU/L, respectively). A significant reduction of epididymal sperm count (2.34 million/mL) was noted in treated rats as compared to control group (7.87 million/mL). Histology of testes showed marked atrophy of the testes, which was characterized by disruption of the seminiferous epithelium and atrophy of the Leydig cells. Crude mixture of A. precatorius seed has a negative impact on male reproductive functions. It might be suggested that crude mixture of A. precatorius seeds might have antifertility property for male rats.   Keywords: Abrus precatorius; antifertility; male rat; testosterone. DOI: http://dx.doi.org/10.3329/bjar.v36i1.9234 BJAR 2011; 36(1): 103-109


2018 ◽  
Vol 41 (2) ◽  
pp. 187-194
Author(s):  
Sina Amirnahavandirahbar ◽  
Mohammad Reza Nasirzadeh

Abstract Diabetes is a chronic disease characterized by a disorder in the metabolism of proteins, fats, and carbohydrates. The liver as a non-insulin dependent organ plays an important role in the regulation of blood fat and glucose. Most blood glucose lowering drugs that are introduced for treatment have side effects in long-term consumption. Therefore, to control diabetes and its complications, the use of herbal drugs is widely considered nowadays. The present study investigates the biochemical effects of oleuropein in diabetic male rats. In this study, 30 adult male Wistar rats with a weight range of 190±30 gr were equally divided into 3 groups randomly: 1) control group or intact animals, 2) diabetic animals, and 3) treatment group, which received 60 mg/kg oleuropein for 30 days by gastric gavage. Diabetes was induced in diabetic and treatment groups by injection of streptozotocin (60 mg/kg) intraperitoneally. At the end of the treatment, the levels of triglyceride, cholesterol, LDL, HDL, VLDL, blood glucose, HbA1C, and activity of AST and ALT were determined. The results showed that the serum lipid profile and blood glucose increased significantly in the diabetic group compared with the control group (p<0.05). Also, HbA1C and atherogenic index decreased significantly in the treatment group compared with the diabetic group (p<0.05). This study showed that oral administration of oleuropein has hypoglycemic effects, which can reduce the serum levels of the lipids profile and the atherogenic index in streptozotocin-induced diabetic male rats.


2006 ◽  
Vol 43 (1) ◽  
pp. 55-58
Author(s):  
Ariney Costa de Miranda ◽  
Paulo Engler Pinto Jr. ◽  
Sidney Resende Ribeiro ◽  
Samson Henrique Bromberg ◽  
Fábio Pinatel Lopasso ◽  
...  

BACKGROUND: Glutamine has been widely used in treatment of small bowel syndrome and its metabolic effects on the small intestine are well known, however, it has been little studied its effects on hepatic metabolism under this condition. AIM: To verify through experimental model, a glutamine based supplemental diet, administered via oral to rats submitted to massive intestinal resection, evaluating weight evolution and hepatic glycogen content. MATERIAL AND METHODS: Male rats, Wistar, were allocated into three groups to undergo enterectomy. Following diets were applied: with glutamine (G group), without glutamine (NG group), and standard diet from the laboratory (R group). All animals had massive small intestine resection including ileocecal valve removal. After 20 days, all animals were sacrificed. The liver was removed to histological analysis by light microscopy. Slides were stained by periodic acid of Schiff with diastasis. RESULTS: All animals lost weight from the beginning to the end of experiment. Comparing weight loss average expressed in percentage, there was no difference statistically significant on this variance. In analyzed groups, the hepatic glycogen content did not differ statistically, in the histological method evaluated. CONCLUSION: Glutamine feeding via oral did not influence weight loss reduction of animal submitted to massive intestinal resection and did not stimulate glycogen synthesis and storage into hepatocytes.


1976 ◽  
Vol 81 (1) ◽  
pp. 198-207 ◽  
Author(s):  
H. L. Verjans ◽  
K. B. Eik-Nes

ABSTRACT Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat.


2020 ◽  
Vol 26 (1) ◽  
pp. 54-67
Author(s):  
Mohammad Mehdi Padam ◽  
◽  
Ameneh Khoshvaghti ◽  

Aims: Damage to liver tissue and its dysfunction is very important and if left untreated, it can cause serious problems and even death. In this study, we aimed to investigate the effects of the hydroalcoholic extracts of Linum usitatissimum and Rosa damascena on liver enzymes, total protein, bilirubin, albumin, and serum glucose levels. Materials and Methods: This is a non-randomized clinical trial conducted on 42 male rats divided into 6 groups; control group (group 1) received only sufficient water and food, groups 1 and 2 received 300 and 500 mg/ kgB.W Linum usitatissimum extract, groups 3 and 4 received 500 and 1000 mg/ kgB.W Rosa damascena, and group 6 received 100 mg/ kgB.W Linum usitatissimum plus 250 mg/ kgB.W Rosa damascena extracts intraperitoneally for 28 days. After the last injection, the rats were weighed and their blood samples were collected. The study parameters were measured using a colorimetric method by a spectrophotometer, and then were analyzed using ANOVA and Tukey’s test in SPSS V. 25 at a significance level of P<0.05. Findings: There was no significant difference between alanine aminotransferase, alkaline phosphatase, total and direct bilirubin levels in the control group in comparison with other groups (P>0.05). In the groups received Rosa damascena extract, there was a significant difference between total protein and albumin levels compared to the control group (P<0.05). Moreover, there was a significant difference between serum glucose and aspartate aminotransferase in the control group compared to other groups (P<0.05). Conclusion: Linum usitatissimum and Rosa damascena have no negative effect on the liver function. The probability of diarrhea occurrence and the possible effects on the total protein and serum albumin after using Rosa damascena, and the effects of different doses of Linum usitatissimum on the glucose levels should be taken into account.


2020 ◽  
Author(s):  
Dilidaer Xilifu ◽  
Alimu Kateer ◽  
Nijiati Rehemu ◽  
Zhao-yong Li ◽  
jie Jiang ◽  
...  

Abstract Background: Hyperuricemia is the most important risk factor for gout, hypertension, coronary artery disease and other cardiovascular diseases. The incidence of hyperuricemia gradually increased in recent years and it is very necessary to explore the medications of the prevention and treatment of hyperuricemia using hyperuricemia animal models. Objective: The objective of present study is to explore the optimal dose of yeast extract and oteracil potassium in the establishment of hyperuricemia rat model. Method: Sixty-four male rats were randomly divided into 8 experimental groups. Rats were treated with yeast extract by intraperitoneal injection or yeast extract by intraperitoneal injection combined with various doses of oteracil potassium by intragastric feeding or intraperitoneal injection for 28 days. The serum uric acid, urea nitrogen and creatinine levels of different groups were measured at 0th day, 7th day, 14th day, 21th day and 28th day. Results: The serum levels of uric acid in the groups of intraperitoneal injection with yeast extract alone, yeast extract by intraperitoneal injection combined with 50-200 mg/kg oteracil potassium by intragastric feeding and yeast extract by intraperitoneal injection combined with 50-100 mg/kg oteracil potassium by intraperitoneal injection were higher than that in the control group. But we found no significant effect on rat kidney, heart or artery in the above groups. In the group of yeast extract by intraperitoneal injection combined with 200 mg/kg oteracil potassium by intraperitoneal injection, we observed the significantly high level of serum uric acid and morphological and pathological changes in rat kidney, heart and artery. Conclusion: In the present study, we found that continuously treated with yeast extract combined with oteracil potassium is an effective method to establish rat hyperuricemia model. Intraperitoneal injection of yeast extract combined with 200 mg/kg oteracil potassium is an optimal dosage for the construction of a persistent and stable hyperuricemia animal model.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M M Elshawwa

Abstract Background Obesity is associated with insulin resistance, type2 diabetes, dyslipidemia and cardiovascular diseases. Apelin and chemerin are identified as adipokines and adipose tissue markers. Several adipose-derived peptides are known to influence food intake, including apelin, whose expression is regulated by insulin and chemerin. Oxidative stress thought to be involved in the development of complications associated with obesity. Objective To study the nature of correlation between serum and liver levels of apelin, chemerin and oxidative parameters in obese rats with and without antioxidant. Aiming to clarify the pathophysiology of obesity. Material and Methods Thirty adult male albino rats, divided into three equal groups. Group I (control), group II (obese) and group III (obese and Lepidium sativum (LS) as an antioxidants). At the end of the experiment, blood samples were collected for estimation of the serum levels of chemerin, apelin, fasting glucose, insulin, insulin resistance (IR), lipid profile, reduced glutathione (GSH) and malondialdehyde (MDA). In addition to tissue homogenous extracts of liver were taken for the levels of MDA, CAT, chemerin and apelin. Results After eight weeks, high fat diet group showed a significant increase in serum levels of apelin, chemerin, fasting glucose, insulin, IR, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) & MDA and a significant decrease in high-density lipoprotein cholesterol (HDL-C) & GSH. HFD also caused a significant increase in tissue levels of MDA, CAT & chemerin and a significant decrease in apelin, compared to control group. While addition of LS to HFD caused a significant decrease in serum levels of apelin, chemerin, fasting glucose, insulin, IR, TC, TG, LDL-C & MDA and a significant increase in HDL-C & GSH. LS also caused a significant decrease in tissue levels of MDA, chemerin & insignificant decrease in CAT and a significant increase in apelin, compared to HFD group. Conclusion This study showed a significant positive correlation between liver & serum chemerin and between liver and serum MDA. On the other hand, it showed a significant negative correlation between liver and serum apelin and liver CAT and serum GSH


2019 ◽  
Vol 8 (5) ◽  
pp. 741-753 ◽  
Author(s):  
Israa F. Mosa ◽  
Mokhtar I. Yousef ◽  
Maher Kamel ◽  
Osama F. Mosa ◽  
Yasser Helmy

Abstract Hydroxyapatite nanoparticles (HAP-NPs) are an inorganic component of natural bone and are mainly used in the tissue engineering field due to their bioactivity, osteoconductivity, biocompatibility, non-inflammatory, and non-toxicity properties. However, the current toxicity data for HAP-NPs regarding human health are limited, and only a few results from basic studies have been published. Therefore, the present study was designed to investigate the beneficial role of chitosan nanoparticles (CsNPs) and curcumin nanoparticles (CurNPs) in alleviating nephrotoxicity induced by HAP-NPs in male rats. The results showed that HAP-NPs caused a reduction in antioxidant enzymes and induced lipid peroxidation, nitric oxide production and DNA oxidation. Moreover, HAP-NP administration was associated with intense histologic changes in kidney architecture and immunoreactivity to proliferating cell nuclear antigen (PCNA). However, the presence of CsNPs and/or CurNPs along with HAP-NPs reduced the levels of oxidative stress through improving the activities of antioxidant enzymes. Also, the rats administered the nanoparticles showed a moderate improvement in glomerular damage which matched that of the control group and showed mild positive reactions to PCNA–ir in glomeruli and renal tubules in the cortical and medullary portions. These novel insights confirm that the presence of chitosan and curcumin in nanoforms has powerful biological effects with enhanced bioactivity and bioavailability phenomena compared to their microphase counterparts. Also, they were able to ameliorate the nephrotoxicity induced by HAP-NPs.


2020 ◽  
Vol 19 (1) ◽  
pp. 121-127
Author(s):  
Ebtisam A. Marzook ◽  
Fawzy A. Marzook ◽  
Ahmed E. Abd El Moneim

Purpose: To evaluate the possible radioprotective effect of Costus speciosus and carnosine as natural antioxidants in order to control the  hyperglycemia developed in male albino rats exposed to acute oxidative stress induced by gamma radiation. Methods: Twenty-eight adult male albino rats were divided into four groups. The first group was taken as a control group, while the three other groups were exposed to Ɣ irradiation at a single 7.5 Gy dose. Furthermore, the rats in the second and third groups were i.p. injected with Costus speciosus root powder and carnosine, respectively. On the 3rd day, after irradiation, the serum levels of glucose, insulin, C peptide, copper, iron, calcium, total antioxidant capacity (TAC) and malondialdehyde (MDA) were measureded. Results: The results revealed that exposure to Ɣ irradiation induced significant increases in serum glucose, iron, and malondialdehyde. However, the levels of serum calcium, copper, total antioxidant capacity and insulin significantly decreased (p < 0.05). A significant decrease was observed in Cpeptide in the exposed group, compared to control group. All the test parameters indicate improvement after treatment with Costus speciosus and carnosine (p < 0.05). Conclusion: Costus speciosus and carnosine ameliorate the effect of gamma radiation, indicating their role as antidiabetic agents and  radioprotectors; however, Costus speciosus was critically more efficient than carnosine. Keywords: Costus speciosus, Carnosine, Diabetes, Insulin, Gamma radiation protection


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Minji Park ◽  
Yuri Choi ◽  
Hyeonhae Choi ◽  
Ju-Yearn Yim ◽  
Jaesook Roh

Prenatal caffeine exposure adversely affects the development of the reproductive organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine exposure would also influence physiologic gonadal changes and function during this critical period for sexual maturation. This study investigated the impact of high doses of caffeine on the testes of prepubertal male rats. A total of 45 immature male rats were divided randomly into three groups: a control group and 2 groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4 weeks. Caffeine caused a significant decrease in body weight gain, accompanied by proportional decreases in lean body mass and body fat. The caffeine-fed animals had smaller and lighter testes than those of the control that were accompanied by negative influences on the histologic parameters of the testes. In addition, stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine consumption can interfere with the maturation and function of the testis, possibly by interrupting endogenous testosterone secretion and reducing the sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we confirmed that pubertal administration of caffeine reduced testis growth and altered testis histomorphology.


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