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1.
Int Immunopharmacol ; 127: 111414, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38141404

ABSTRACT

5-androstenediol (ADIOL) functions as a selective estrogen receptor ß (ERß) ligand with a protective effect against many diseases. So, we conducted a novel insight into its role in acetic acid (AA)-induced colitis and investigated its effect on TLR4-Mediated PI3K/Akt and NF-κB Pathways and the potential role of ERß as contributing mechanisms. METHODS: Rats were randomized into 5 Groups; Control, Colitis, Colitis + mesalazine (MLZ), Colitis + ADIOL, and Colitis + ADIOL + PHTPP (ER-ß antagonist). The colitis was induced through a rectal enema of acetic acid (AA) on the 8th day. At the end of treatment, colons were collected for macroscopic assessment. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor kappa b (NF-κB), toll-like receptor (TLR4), and phosphorylated Protein kinase B (pAKT) were measured. Besides, Gene expression of interleukin-1beta (IL-1ß), metalloproteases 9 (Mmp9), inositol 3 phosphate kinase (PI3K), Neutrophil gelatinase-associated lipocalin (NGAL), ERß and NLRP6 were assessed. Histopathological and immunohistochemical studies were also investigated. RESULTS: Compared to the untreated AA group, the disease activity index (DAI) and macroscopic assessment indicators significantly decreased with ADIOL injections. Indeed, ADIOL significantly decreased colonic tissue levels of MDA, TLR4, pAKT, and NF-κB immunostainig while increased SOD activity and ß catenin immunostainig. ADIOL mitigated the high genetic expressions of IL1ß, NGAL, MMP9, and PI3K while increased ERß and NLRP6 gene expression. Also, the pathological changes detected in AA groups were markedly ameliorated with ADIOL. The specific ERß antagonist, PHTPP, largely diminished these protective effects of ADIOL. CONCLUSION: ADIOL could be beneficial against AA-induced colitis mostly through activating ERß.


Subject(s)
Colitis , NF-kappa B , Rats , Male , Animals , NF-kappa B/metabolism , Rats, Wistar , Estrogen Receptor beta/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Toll-Like Receptor 4/metabolism , Lipocalin-2 , Matrix Metalloproteinase 9/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Acetic Acid/adverse effects , Androstenediol/adverse effects , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Superoxide Dismutase/metabolism
2.
Anat Sci Int ; 98(1): 22-35, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35507276

ABSTRACT

Osteoporosis increases bone fragility and fractures. Preptin hormone is regulated by moderate exercise training and increases bone formation. Therefore, this study was conducted to see how estradiol administration and moderate exercise training affected osteoporotic changes in ovariectomized (OVX) rats. To achieve this aim, 36 healthy adult female Wistar albino rats were randomized into Sham, OVX, ovariectomized estradiol-treated (OVX + E) (OVX + E rats were treated using subcutaneous estradiol benzoate 2.5 µg/kg body weight/day), ovariectomized practicing moderate exercise training, ovariectomized estradiol-treated and practiced a moderate exercise training, and ovariectomized alendronate-treated (OVX + Alen) (OVX + Alen rats were treated orally with alendronate 3 mg/kg body weight/week) groups. Alendronate was used as a standard anti-osteoporotic drug. Moderate exercise training, including therapy with estradiol and alendronate for OVX rats began on the fourth week and lasted for six weeks. Results showed that OVX rats had estrogen and preptin deficiency in serum. These deficiencies were associated with a significant increase in bone resorption biomarkers (urinary deoxypyridinoline and hydroxyproline), and bone formation biomarkers (serum osteocalcin and bone-specific alkaline phosphatase). Also, serum pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) were increased, while bone osteopontin (OPN) expression was decreased. Subsequently, the osteoporotic alterations were verified based on histopathological changes. From the results, estradiol therapy and moderate exercise training significantly improved these findings to the same extent as that of the standard alendronate treatment. Therefore, through their anti-inflammatory properties, increasing bone OPN expression, and regulating serum preptin; estradiol therapy and moderate exercise training can reduce osteoporotic alterations in OVX rats. Thus, combined estradiol therapy and moderate exercise training could be a promising potential therapeutic protocol to reduce postmenopausal osteoporosis. Also, targeting serum preptin and bone osteopontin regulation could have a critical role in the treatment of postmenopausal osteoporosis.


Subject(s)
Bone Density , Osteoporosis, Postmenopausal , Animals , Humans , Rats , Female , Alendronate/pharmacology , Alendronate/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Osteopontin , Rats, Wistar , Estradiol/pharmacology , Body Weight , Biomarkers , Ovariectomy
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