Investigation of the effect of COVID-19 on sperm count, motility, and morphology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus that causes many diseases such as respiratory diseases, cardiovascular diseases, and gastrointestinal diseases. Although it has been shown that the angiotensin-converting enzyme 2 receptor, which has a high affinity for the SARS-CoV-2 is mostly expressed in the lungs, it is also expressed especially in the cells of the testicular tissue. Although there are studies showing the effect of SARS-CoV-2 on spermatogenesis, the effects of COVID-19 on sperm count, motility, and morphology are still unclear. The aim of this study is to investigate changes in sperm quality in men who had recovered and never had COVID-19, therefore semen samples were analyzed from all individuals in the patient and control groups aged 20-50 years who agreed to participate in the study and voluntary in SBU Ministry of Health Adana City Training and Research Hospital. (Toros University Ethics Committee Decision Number: 1433, Date: April 15, 2021) (Adana Provincial Health Directorate Ethics Commission Decision dated May 27, 2021/5). Two groups were selected (100 men had and recovered from COVID-19, and 100 men never had COVID-19) spermiograms from both groups were analyzed in accordance with the World Health Organization standards. The sperm concentration of the COVID-19 negative group was significantly higher than those in the COVID-19 positive group. No statistically significant difference was detected between the groups for sperm motility and morphology. It was observed that men with COVID-19 had decreased sperm concentrations suggesting that COVID-19 may have a negative effect on male fertility. However, in the long term, more comprehensive studies with a large sample size are needed to understand better the changes in sperm concentration.

ß-Hydroxybutyrate, One of the Three Main Ketone Bodies, Ameliorates Acute Pancreatitis in Rats by Suppressing the NLRP3 Inflammasome Pathway.

BACKGROUND: Acute pancreatitis (AP) is a widespread disease resulting from the inflammation of acinar cells in the pancreas. ß-hydroxybutyrate (BHB) is a water-soluble main ketone body synthesized in the human liver. The purpose of this study was to examine the possible therapeutic effects of BHB in the experimentally-induced AP model in rats. METHODS: In our study, male rats were randomly allotted into 6 groups, as control (0.9% saline i.p.), BHB1 (200 mg/kg BHB i.p.), BHB2 (2 doses of 200 mg/kg BHB i.p.), AP (4 doses of 50 µg/kg cerulein i.p., 4 doses at 1 h intervals), AP+BHB1 and AP+BHB2 groups. In pancreatic tissue sections, immunohistochemistry staining and western blot analysis for the inflammasome complex (caspase-1, ASC, and NLRP3) and inflammation-associated proteins (TNF-α and NF-κB) and a histopathological examination were performed. The levels of lipase, amylase, interleukin (IL)-18 and IL-1ß in serum were measured. RESULTS: Several pathological degenerations, including edema, inflammatory cell infiltration, acinus necrosis, and bleeding were observed in the AP group, while the histological architecture of the control and the sham BHB1 and BHB2 groups were regular. The AP-induced pathological changes were considerably alleviated in the AP+BHB1 and AP+BHB2 groups. In the AP group, a conspicuous increase in caspase-1, ASC, NLRP3, TNF-α, and NF-κB proteins, and in the levels of amylase, lipase, IL-18, and IL-1ß were detected. BHB treatments after AP induction decreased those proteins to the level of control. CONCLUSIONS: We demonstrated that BHB has the potential to cure AP by suppressing the NLRP3 inflammasome and can be used in the treatment of many diseases which progress through the NLRP3 inflammasome.

Cardiac hypertrophy caused by hyperthyroidism in rats: the role of ATF-6 and TRPC1 channels.

Hyperthyroidism influences the development of cardiac hypertrophy. Transient receptor potential canonical channels (TRPCs) and endoplasmic reticulum (ER) stress are regarded as critical pathways in cardiac hypertrophy. Hence, we aimed to identify the TRPCs associated with ER stress in hyperthyroidism-induced cardiac hypertrophy. Twenty adult Wistar albino male rats were used in the study. The control group was fed with standard food and tap water. The group with hyperthyroidism was also fed with standard rat food, along with tap water that contained 12 mg/L of thyroxine (T4) for 4 weeks. At the end of the fourth week, the serum-free triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) levels of the groups were measured. The left ventricle of each rat was used for histochemistry, immunohistochemistry, Western blot, total antioxidant capacity (TAC), and total oxidant status (TOS) analysis. As per our results, activating transcription factor 6 (ATF-6), inositol-requiring kinase 1 (IRE-1), and TRPC1, which play a significant role in cardiac hypertrophy caused by hyperthyroidism, showed increased activation. Moreover, TOS and serum-free T3 levels increased, while TAC and TSH levels decreased. With the help of the literature review in our study, we could, for the first time, indicate that the increased activation of ATF-6, IRE-1, and TRPC1-induced deterioration of the Ca2+ ion balance leads to hypertrophy in hyperthyroidism due to heart failure.

Investigation of the effect of hyperthyroidism on endoplasmic reticulum stress and tran- sient receptor potential canonical 1 channel in the kidney

Background/aim: Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angio- tensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are gluco- se-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1). Materials and methods: Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also im- munohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies. Results: TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analy- sis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05). Conclusion: In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.

Protective effect of carnosic acid on acrylamide-induced liver toxicity in rats: Mechanistic approach over Nrf2-Keap1 pathway.

Acrylamide is a food contaminant with a range of toxic effects. Carnosic acid (C20 H28 O4 ) is a phenolic compound found in plants and has many beneficial effects. In this study, we aimed at investigating the effect of carnosic acid on acrylamide-induced liver damage. Rats (n = 7) were allotted to control, carnosic acid, acrylamide, acrylamide + carnosic acid groups. Animals were euthanized. Their blood was taken for biochemical analysis, and liver tissue was excised for morphological, immunohistochemical, and immunoblotting analyses. As a result, acrylamide reduced bodyweight, liver weight, catalase, and total antioxidant capacity levels but increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total oxidant status, oxidative stress index levels, Nrf2, and Keap1 protein levels. In addition, acrylamide disrupted liver histology leading to vascular congestion, cellular infiltration, necrotic cells, and so forth. Carnosic acid cotreatment ameliorated the altered biochemical parameters, liver histology, Nrf2, and Keap1 enzyme levels. In conclusion, carnosic acid has the potential to be used as a protective agent against acrylamide-induced liver damage.

Silymarin attenuated nonalcoholic fatty liver disease through the regulation of endoplasmic reticulum stress proteins GRP78 and XBP-1 in mice.

Nonalcoholic fatty liver disease (NAFLD) is an important health problem. The prevalence of NAFLD is increasing, especially in the Western countries. Although there are several intracellular pathways in NAFLD, endoplasmic reticulum (ER) stress has recently gained importance. Silymarin is an important liver-protective biological molecule. In light of this information, we investigated mice for the effect of silymarin on ER stress in the NAFLD model. In our study, the mice were randomly divided into six groups: Control, silymarin 100 and 200 mg/kg sham, fructose-induced NAFLD, and NAFLD + silymarin groups. After the last administrations, liver and blood samples were taken and hematoxylin-eosin, as well as Oil red O staining, were performed. As a result, the body and liver weights, lipid profile, AST, ALT, and glucose levels, along with the ER stress markers, increased in the NAFLD-only group. Silymarin treatments reversed most of these changes. Particularly, 200 mg/kg silymarin was more effective. PRACTICAL APPLICATIONS: According to the results, silymarin attenuated NAFLD by decreasing the ER stress proteins GRP78 and XBP-1. Silymarin may be therapeutic in the treatment of NAFLD as well as other ER-stress-based diseases. Silymarin can also be taken with food for prophylactic purposes.

Azoramide ameliorates fructose-induced nonalcoholic fatty liver disease in mice.

Nonalcoholic fatty liver disease (NAFLD) is a frequent health problem. The insulin resistance and endoplasmic reticulum (ER) stress have been suggested to play important roles in the development and progression of NAFLD. However these processes and correlations have not fully been understood yet. Azoramide, an antidiabetic drug, has the potential for reducing insulin resistance and ER stress in obese mice. To date, there is no study on the effects of azoramide in NAFLD. The aim of this study was to investigate the potential role of azoramide on insulin resistance and ER stress in NAFLD induced mice. Forty Swiss Albino mice were assigned into control, azoramide, fructose and fructose + azoramide groups. Azoramide group received a single dose of azoramide at 150 mg/kg/day by gavage between 71-77th days. Fructose group was treated with 30% fructose solution for 70 days to generate NAFLD. Fructose + azoramide group was treated with 30% fructose for 70 days and then with a single dose of 150 mg/kg/day azoramide for 7 days. At the end of experiment, blood of mice was taken via cardiac puncture, and the livers were excised and weighted. GRP78 and XBP-1 levels were examined with immunohistochemistry in liver tissues. Liver steatosis was evaluated with H&E, Oil-Red O and Sudan-Black staining. ALT, AST, triglyceride, total cholesterol, VLDL, LDL, HDL, fasting glucose and insulin levels were measured in serum. The body and liver weights, insulin resistance, ER-stress markers, lipid profile, AST, ALT and histopathological changes increased by fructose treatment. Azoramide treatment was generally reversed all these changes. These data offer the first evidence to show that azoramide may serve as a potential treatment agent in NAFLD through decreasing the ER-stress and insulin resistance.