The Hepatic Antisteatosis Effect of Xanthohumol in High-Fat Diet-Fed Rats Entails Activation of AMPK as a Possible Protective Mechanism.

Obesity is the leading cause of non-alcoholic fatty liver disease by provoking hyperglycemia, hyperlipidemia, insulin resistance, oxidative stress, and inflammation. Low activity of AMP-activated protein kinase (AMPK) is linked to obesity, liver injury, and NAFLD. This study involves examining if the anti-steatosis effect of Xanthohumol (XH) in high-fat diet (HFD)-fed rats involves the regulation of AMPK. Adult male rats were divided into five groups (n = 8 each) as control (3.85 kcal/g); XH (control diet + 20 mg/kg), HFD (4.73 kcl/g), HFD + XH (20 mg/kg), and HFD + XH (30 mg/kg) + compound c (cc) (0.2 mg/kg). All treatments were conducted for 12 weeks. Treatment with XH attenuated the gain in body weight, fat pads, fasting glucose, and insulin in HFD rats. It also lowered serum leptin and free fatty acids (FFAs) and improved glucose and insulin tolerances in these rats. It also attenuated the increase in serum livers of liver marker enzymes and reduced serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), FFAs, as well as serum levels of low-density lipoproteins cholesterol (LDL-c) oxidized LDL-c. XH also reduced hepatic levels of malondialdehyde (MDA), nuclear accumulation of NF-κB, and the levels of tumor necrosis-factor-α (TNF-α) and interleukin-6 (IL-6) while stimulating the nuclear levels of Nrf2 and total levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in these HFD-fed rats. At the molecular levels, XH increased hepatic mRNA expression and phosphorylation of AMPK (Thr72) and reduced the expression of lipogenic genes SREBP1c and ACC-1. In concomitance, XH reduced hepatic liver droplet accumulation, reduced the number of apoptotic nuclei, and improved the structures of nuclei, mitochondria, and rough endoplasmic reticulum. Co-treatment with CC, an AMPK inhibitor, completely abolished all these effects of XH. In conclusion, XH attenuates obesity and HFD-mediated hepatic steatosis by activating hepatic AMPK.

Therapeutic Potential of Mesenchymal Stem Cells versus Omega n - 3 Polyunsaturated Fatty Acids on Gentamicin-Induced Cardiac Degeneration.

This study compared the cardioprotective action of mesenchymal stem cells (MSCs) and PUFAs in a rat model of gentamicin (GM)-induced cardiac degeneration. Male Wistar albino rats were randomized into four groups of eight rats each: group I (control group), group II (gentamicin-treated rats receiving gentamicin intraperitoneally (IP) at dose of 100 mg/kg/day for 10 consecutive days), group III (gentamicin and PUFA group receiving gentamicin IP at dose of 100 mg/kg/day for 10 consecutive days followed by PUFAs at a dose of 100 mg/kg/day for 4 weeks), and group IV (gentamicin and MSC group receiving gentamicin IP at dose of 100 mg/kg/day followed by a single dose of MSCs (1 × 106)/rat IP). Cardiac histopathology was evaluated via light and electron microscopy. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), caspase-3 (apoptosis), Bcl2, and Bax expression was performed. Moreover, cardiac malonaldehyde (MDA) content, catalase activity, and oxidative stress parameters were biochemically evaluated. Light and electron microscopy showed that both MSCs and PUFAs had ameliorative effects. Their actions were mediated by upregulating PCNA expression, downregulating caspase-3 expression, mitigating cardiac MDA content, catalase activity, and oxidative stress parameters. MSCs and PUFAs had ameliorative effects against gentamicin-induced cardiac degeneration, with MSCs showing higher efficacy compared to PUFAs.

Protective effect of tetrahydrobiopterin on hepatic and renal damage after acute cadmium exposure in male rats.

Cadmium (Cd) has been recognized as one of the most important environmental and industrial pollutants. This study investigated the impact of acute exposure to Cd on oxidative stress and the inflammatory marker interleukin-6 (IL-6) in the plasma of rats and the histological picture of liver and kidney, as well as to examine the potential protective effect of tetrahydrobiopterin (BH4). METHODS: Rats were divided into control group, Cd group that received a single intraperitoneal (i.p.) dose of 4 mg/kg b.w. of CdCl2 and BH4+ Cd group that received a single dose of BH4 (20 mg/kg, i.p.) and subsequently exposed to a single dose of Cd 24 h after the BH4 treatment. RESULTS: Cd increased the plasma levels of hepatic enzymes (ALT and AST), urea, creatinine, malondialdehyde (MDA), and IL-6 and decreased the superoxide dismutase (SOD) activity. Also, it induced histopathological alterations in the liver with severe degeneration, especially in centrilobular zones. Renal tubular epithelium showed vacuolated cytoplasm and dense nuclei. VEGF expression was mild. Ultrastuctural changes were seen in some renal tubules. The nuclei appeared distorted with electron dense chromatin. Mitochondria with destructed cristae were observed. BH4 pretreatment had protective effects, since it significantly reduced the levels of IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Improvement of histopathological alterations was observed in Cd-groups. The nuclei were vesicular euchromatic, intact mitochondria and normal appearance of the filtration membrane. Moderate expression of VEGF was noted. CONCLUSION: This study has provided clear evidence for the protective efficacy of BH4 against experimental Cd toxicity.

Ultrastructural Features of Eutopic Endometrium in a Rat Model of Endometriosis.

Endometriosis is a chronic recurrent disease that is relatively common. Diagnosis is difficult and often delayed. Current treatments are inadequate with unacceptable side effects and multiple surgeries may be needed. Abnormal eutopic endometrium may play important role in endometriosis-associated infertility. This study aimed to examine the ultrastructural changes in eutopic endometrium in a rat model of surgically induced endometriosis. Endometrial tissue was removed from rats in surgical endometriosis induction group (n = 10), sham operated (n = 10) and non-operated control (n = 10) groups in the diestrus phase of the estrus cycle. They were studied with light, transmission and scanning electron microscope as well as morphometric analysis. Eutopic endometrium in surgically induced endometriosis showed pseudostratified epithelium, vacuolated columnar cells alternated with dark cells. The stroma was edematous exhibiting dilated, congested blood vessels. The mean endometrial mucosal depth and surface epithelial height significantly increased. Ultrastructurally, most luminal epithelial cells showed vacuolation. Mucous secretory granules were surrounded by dilated rough endoplasmic reticulum cisternae. Mitochondria, glycogen deposits and vesicles with electron dense cores were observed. The nuclei were highly euchromatic. Well defined microvilli were noticed with evident apical tight junctions. Scanning electron microscope revealed flattened and structurless surface epithelium with apparent decrease in the number of pinopodes. A different response to sex hormones in different parts of eutopic endometrium was observed. Ultrastructural features of estrogen dominance or progesterone resistance in the eutopic endometrium might account for inappropriate cyclic changes occurring in the disease.