Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1.

BACKGROUND: This study aimed to explore the impact of Diacerein (DIC) on endocrine and cardio-metabolic changes in polycystic ovarian syndrome (PCOS) mouse model. METHODS: A total of 18 adult female mice (Parkes strain), aged 4-5 weeks, were randomly assigned to three groups, each comprising 6 animals, as follows: Group I (control), received normal diet and normal saline as vehicle for 51 days; Group II received Letrozole (LET; 6 mg/kg bw) for 21 days to induce PCOS; Group III received LET, followed by daily oral gavage administration of DIC (35 mg/kg bw) for 30 days. RESULTS: This study indicates that treatment with LET resulted in PCOS with characteristics such as polycystic ovaries, elevated testosterone, weight gain, visceral adiposity, high levels of insulin as well as fasting blood glucose in addition to insulin resistance, improper handling of ovarian lipids, atherogenic dyslipidemia, impaired Na + /K + -ATPase activity and serum, cardiac, and ovarian oxidative stress. Serum/ovarian adiponectin levels were lowered in LET-treated mice. In mice treated with LET, we also discovered a reduction in cardiac and serum paraoxonase 1 (PON1). Interestingly, DIC restored ovarian andcardio-metabolic abnormalities in LET-induced PCOS mice. DIC prevented the endocrine and cardio-metabolic changes brought on by letrozole-induced PCOS in mice. CONCLUSION: The ameliorative effects of DIC on letrozole-induced PCOS with concurrent oxidative stress, abdominal fat deposition, cardiac and ovarian substrate mishandling, glucometabolic dysfunction, and adiponectin/PON1 activation support the idea that DIC perhaps, restore compromised endocrine and cardio-metabolic regulators in PCOS.

Ameliorative effects of gallic acid on GLUT-4 expression and insulin resistance in high fat diet-induced obesity animal model mice, Mus musculus.

Reduced activity of glucose transporter type 4 isoform (GLUT-4), an insulin-sensitive glucose transporter distributed on the adipocytes, is associated with impaired insulin signaling. Insulin resistance resulting from alteration in glucose transport is responsible for exacerbating the emergence of metabolic abnormalities. The present study aimed to investigate the effects of the antidote gallic acid (GA) on expression-related changes in GLUT-4 and insulin receptor substrate-1 (IRS-1) in the visceral adipose tissue and on the subsequent development of insulin resistance in a high-fat diet (HFD)-induced obesity animal model. Methods: Twenty-four female Swiss albino mice were used and separated into the following four groups (six animals in each group): control group (standard pellet diet), HFD group, (60% HFD), HFD + GA group (60% HFD and GA 50 mg/kg body weight for 60 days), and GA group (GA 50 mg/kg body weight for 60 days). The effect of HFD on serum glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein (LDL) cholesterol, and insulin was evaluated. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) and glucose tolerance test (GTT) was performed. The serum antioxidative profile, which comprises oxidative parameters (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GPx]) was measured. The effectiveness of GA against HFD-induced alteration in GLUT-4 and IRS-1 expression was also evaluated. Results: The experimental group that fed on GA + HFD had improved levels of serum triglycerides (p˂0.001), cholesterol (p˂0.05), and LDL cholesterol. GA administration also significantly improved hyperinsulinemia and HOMA-IR index (p˂0.001) in HFD mice. GA improved GTT results (p˂0.05); activity of SOD, CAT, and GPx (p˂0.05); and upregulated mRNA expression of GLUT-4 and IRS-1(p˂0.05) in the visceral adipose tissue in the HFD + GA experimental group. Conclusion: A link exists between insulin resistance, GLUT-4, and IRS-1 expression in the adipose tissue, and the initiation of metabolic syndrome, a condition characterized by obesity. GA may promote insulin signaling, glucose uptake, and lipid metabolism in the adipose tissues by mitigating oxidative stress. GA can also be used to manage obesity-related comorbidities including type 2 diabetes and dyslipidemia. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01194-5.

Role of diacerein on steroidogenesis and folliculogenesis related genes in ovary of letrozole-induced PCOS mice.

Polycystic ovary syndrome (PCOS), an intricate and multifaceted metabolic-endocrine disorder that typically affects 6-20% of women of reproductive age and accounts for 70-80% of all occurrences of infertility globally. In this study we focussed on the effect of diacerein (DIC) on steroidogenesis and follicle development in addition to the basic metabolic and endocrine problems which are associated with PCOS. Eighteen mature female parkes strain mice were separated into three groups at random with 6 animals in a group as follows: Group I, received water and normal diet for 66 days; group II received letrozole (LETZ) (6 mg/kg bw) for the induction of PCOS; Group III received LETZ (6 mg/kg) for 3 weeks followed by the administration of DIC (35 mg/kg) for 45 days. In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH, estrogen level and decline in expression of Kitl, Bmp, Cyp11a1, CYP19a1, Ar, lhr, Fshr and Esr1 as well as decreased SOD and CAT activity in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in serum cholesterol, triglycerides, testosterone, LH, VEGF and insulin levels. All these changes were reversed after the administration of DIC in PCOS mice. Diacerin administration reversed abnormalities in mice with PCOS by modulating the regulation of genes which are related to steroidogenesis and folliculogenesis.

Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor.

Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6-20% of females. Our study's major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.

Turmeric extract alleviates endocrine-metabolic disturbances in letrozole-induced PCOS by increasing adiponectin circulation: A comparison with Metformin.

One of the most common causes of female infertility is polycystic ovarian syndrome, which affects 6-21% of the population. Regrettably, the currently available treatments are mostly symptomatic and ineffective. As a result, safer options are needed now more than ever. In a letrozole PCOS albino mouse model, the current study compares the therapeutic advantages of Turmeric extract (Curcuma longa) to metformin. Adiponectin is a circulating protein generated by adipocytes that has been linked to metabolic diseases (MDs) in an inverse relationship. The effects of Turmeric Extract (Curcuma Longa) in contrast to Metformin, as well as the involvement of adiponectin in endocrine-metabolic abnormalities in experimentally induced PCOS mice model, were studied in this study. Letrozole (6 mg/kg) was administered orally (p.o) for 21 days to induce PCOS, followed by a dose of Turmeric Extract (Curcuma longa) (175 mg/kg and p.o) and Metformin (150 mg/kg) for 30 days, both with normal saline water (0.9%) as the carrier. The findings revealed that LET-treated mice displayed PCOS-like characteristics, such as higher LH levels, increased body weight growth, and ovarian morphology with numerous cysts, increase in fasting blood glucose, lipid profile, plasma lipid peroxidation (MDA) and IL-6, as well as a decrease in serum Progesterone, Estrogen, FSH, SOD and GSH levels in the ovary. These changes were linked to lower levels of circulating adiponectin and were reversed when treated Turmeric extract. By altering circulating androgen-adiponectin balance, the data implies that Turmeric extract alleviates endocrine-metabolic abnormalities and inflammation-related comorbidities associated with LET-induced PCOS.

Vitamin C mitigates hematological and biochemical alterations caused by di(2-ethylhexyl) phthalate toxicity in female albino mice, Mus musculus.

Di(2-ethylhexyl) phthalate (DEHP) is ubiquitous environmental contaminant and identified as endocrine-disrupting chemical (EDC), present in plastics as plasticizer. Due to its versatile use, human exposure level reaches to danger limit. The main focus of our study is to see the effect of vitamin C on hematological and biochemical alterations caused by Di(2-ethylhexyl) Phthalate toxicity in female albino mice, Mus musculus. It is found to cause defects of the liver, kidney, and lungs. Its anti-androgenic nature brings the main focus on its toxicity associated with reproductive and endocrine system. In this experimental study, 18 young female Swiss albino mice, Mus musculus, were used and divided into 3 groups of 6 animals each as control (corn oil vehicle), DEHP group (100 mg/kg body weight dissolved in corn oil), and DEHP + vitamin-C group (100 mg/kg body weight each, dissolved in corn oil and double distilled water, respectively) for 90 days. In this research, serum metabolites were evaluated to study the effect of DEHP on glucose, total protein, and lipid profile along with some hematological, enzymological, and oxidative stress parameters. Simultaneously, we compared the effectiveness of vitamin-C against DEHP toxicity to mitigate the serum homeostasis disturbance. In present study, we observed, in DEHP-treated animals, glucose, triglycerides, very-low-density lipoprotein (VLDL), total protein, alkaline phosphatase (ALP), acid phosphatase (ACP), and alanine aminotransferase (ALT) levels increased remarkably, whereas total cholesterol, high-density lipoproteins (HDL), aspartate aminotransferase (AST), total RBC count, total WBC count, and hemoglobin (Hb) level significantly decreased as compared to control group. In addition, we noticed there was a decrease in superoxide dismutase (SOD) and increase in levels of lipid peroxidation (MDA) and interleukin-6 (IL-6) in DEHP treatment group as compared to control group. The results indicated vitamin C had a better improving effect against DEHP toxicity on balancing metabolic abnormalities and inflammation-related comorbidities.

Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression.

Research question: Women are increasingly suffering from polycystic ovary syndrome (PCOS). Its pathophysiology is still unknown, though. The purpose of this study was to ascertain how gallic acid affected the pathophysiology of the ovary in an animal model of polycystic ovary syndrome. We also showed the potential mechanism of adiponectin involvement in endocrine metabolic changes in PCOS mice and the function of adiponectin, which appear to be frequent factors in PCOS. Design: Eighteen adult female Parkes strain mice (Age: 4-5 weeks) having body weight of 16-21 g were separated into three groups at random with 6 animals in each group as follows: Group I serving the control, received water and normal diet for 81 days; group II received oral gavage administration of letrozole (LETZ)(6 mg/kg b.w.daily), which was dissolved in 0.9 % NaCl solution for 21 days for the induction of PCOS and left untreated for 60 days; Group III received oral gavage administration of LETZ (6 mg/kg) for first 21 days followed by the administration of gallic acid (GA) (75 mg/kg b.w. orally daily) for 60 days. Results: We found LETZ-treated mice experienced PCOS-like symptoms, including increased Serum testosterone, LH/FSH ratio, body and ovarian weight, blood glucose, serum insulin levels and inflammatory Cytokines. We also found decreased serum estrogen, oxidant capacity and enzyme activity and altered ovarian cytoarchitecture, with multiple cysts apart from irregular estrous cycle. Furthermore, mRNA expression levels CYP11a, CYP19a1, Kitl, PTGS2 and Adipo R1 were decreased. Furthermore, LETZ-induced PCOS mice when treated with GA we observed decrease in testosterone, LH, LH/FSH ratio, blood glucose, serum insulin and inflammatory cytokines. GA treatment in PCOS mice also increased estrogen levels, and oxidant capacity as well as enzyme activity. Furthermore mRNA expression levels of CYP11a1, CYP19a1, KITL, PTGS2 and Adipo R1 were also increased in LETZ+GA treated mice. These changes were linked to lower levels of circulating adiponectin and were altered when the mice were administered with gallic acid. Conclusion: Gallic acid might be a potential therapy in treating PCOS by regulating endocrine and metabolic abnormalities that are brought on by a drop in adiponectin levels along with hyperandrogenism. Additionally, adiponectin seems to be a frequent factor in PCOS. In addition to reducing inflammation-related comorbidities linked to LETZ-induced PCOS, GA enhances mRNA expression levels CYP11a, CYP19a1, Kitl and PTGS2 and hence reduces endocrine and metabolic abnormalities.

Environmental Impact of the Presence, Distribution, and Use of Artificial Sweeteners as Emerging Sources of Pollution.

Artificial sweeteners are posing a new threat to the environment. The water ecosystem is the primary recipient of these emerging contaminants. Once ingested, sufficient amount of these artificial sweeteners escape unchanged from the human body and are added to the environment. However, some are added in the form of their breakdown products through excretion. Artificial sweeteners are resistant to wastewater treatment processes and are therefore continuously introduced into the water environments. However, the environmental behavior, fate, and long-term ecotoxicological contributions of artificial sweeteners in our water resources still remain largely unknown. Some artificial sweeteners like saccharin are used as a food additive in animal feeds. It also forms the degradation product of the sulfonylurea herbicides. All artificial sweeteners enter into the wastewater treatment plants from the industries and households. From the effluents, they finally reside into the receiving environmental bodies including wastewaters, groundwaters, and surface waters. The global production of these sweeteners is several hundred tons annually and is continuously being added into the environment.

Effects of Kamdhenu Ark and Active Immunization by Gonadotropin Releasing Hormone Conjugate (GnRH-BSA) on Gonadosomatic Indices (GSI) and Sperm Parameters in Male Mus musculus.

BACKGROUND: Active immunization against GnRH decreases the secretion of gonadotropins and causes cessation of gonadal function, thereby, inducing infertility. Based on the immunoenhancing activity of Kamdhenu ark (distilled cow urine), this study was performed to evaluate its effects on the gonadosomatic indices (GSI) and sperm parameters in male mice receiving a GnRH contraceptive vaccine. METHODS: Sixty adult male mice of Parke's strain were divided into three groups of twenty. Group I served as the controls, while group II was immunized by GnRH-BSA conjugate (50/0.2/35 µg/ml/g BW) by four intraperitoneal injections at different intervals on days 1, 30, 60 and 90. However, group III was supplemented daily by oral Kamdhenu ark (100 ppm) along with GnRH-BSA immunizations. The animals were sacrificed after 30, 60, 90 and 120 days and their testis and epididymis were dissected out weighed and semen analysis was performed. RESULTS: GSI values, sperm motility, sperm count and sperm morphology in male Mus musculus were decreased significantly in all the experimental groups as compared to the control group (p<0.01). Kamdhenu ark significantly enhanced the effect of GnRH vaccine on the aforesaid parameters especially in 90 and 120 days treated groups (p<0.05). CONCLUSION: The changes witnessed in sperm parameters suggested that the GnRH-BSA immunization suppressed the activities of gonadotropins and testosterone directly through hypothalamo-hypophysial-gonadal axis and indirectly by acting on the testes which may modulate the sperm morphology, sperm count and motility. However, Kamdhenu ark seems to have enhanced these effects because of its immune-modulatory properties too.