Possible protective role of L-thyroxin on the parotid gland of adult male albino rat in carbimazole induced hypothyroidism: histological, histomorphometry, and ultrastructural study.

BACKGROUND: Thyroid disorders are among the most common metabolic disorders worldwide. Thyroid dysfunction affects salivary glands function, causing hyposalivation. It also provokes physiological and histological changes in parotid, submandibular, and in particular the sublingual gland. THE AIM OF THIS WORK: The aim of this work was to clarify the histological and ultrastructural changes that occur in the parotid gland following carbimazole-induced hypothyroidism in adult male albino rats. The study also aims to investigate the possible protective role of L-thyroxin supplementation on the rat parotid glands after long and short duration of hypothyroidism. MATERIAL AND METHODS: Fifty-five adult male albino rats of Sprague Dawley strain; were divided into four groups and eleven subgroups, five rats each. G І received nothing. G П given normal saline orally daily. G Ш (medical Hypothyroidism, short duration - long duration - recovery group) given Carbimazole orally by gastric tube in a dose of 0.05 mg/kg daily for 3,6 successive weeks for group (a, b) and for 6 successive weeks then were left without any medication for another 3 weeks in recovery group c. G IV-b, c (L-Thyroxine supplemented group, short duration-long duration) given Carbimazole orally daily for 3,6 successive weeks then L-thyroxine was given orally in a dose of (10 µg/100 g/B.W) daily for another 3 successive weeks. Animals were sacrificed 24 hours after the last dose of Carbimazole in G III-a, b and 3 weeks after stoppage the drug in G III-c. Animals were sacrificed 24 hours after the last dose of L- Thyroxine in G IV-b, c. The parotid specimens were processed for histopathological examination by light and electron microscopy. The medically induced Hypothyroidism resulted in significant parotid gland damage which was more obvious with longer duration; as follow: a) most of the acini had irregular outlines and were widely separated with narrow lumen and cytoplasmic vacuoles. b) some acinar cells contained ill defined, irregular, pyknotic or hyperchromatic nuclei. c)Vascular changes: dilated and engorged with blood. d) the interlobular and striated ducts appeared disrupted and dilated. e) extravasated blood with cellular infiltration were seen in the interstitial space. IN CONCLUSION: Thyroid hormones (THs) had a significant effect in protection of parotid gland against damage induced by carbimazole, as it preserved the normal histological architecture of the parotid gland. This beneficial effect of THs was mostly related to its antioxidant properties. The expression of BCL-2 has certain regularity in apoptosis after drug administration. Regulation of glandular atrophy and apoptosis are closely related. The molecular mechanism of the apoptosis of the gland is not clear, and further study is needed in the future.

lnc-HOTAIR predicts hepatocellular carcinoma in chronic hepatitis C genotype 4 following direct-acting antivirals therapy.

Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.