Nicotine exacerbates liver damage in a mice model of Ehrlich ascites carcinoma through shifting SOD/NF-κB/caspase-3 pathways: ameliorating role of Chlorella vulgaris.

Nicotine, a pervasive global environmental pollutant, is released throughout every phase of the tobacco's life cycle. This study examined the probable ameliorative role of Chlorella vulgaris (ChV) extract against nicotine (NIC)-induced hepatic injury in Ehrlich ascites carcinoma (EAC) bearing female Swiss mice. Sixty female Swiss mice were assigned to four equal groups orally gavaged 2% saccharin 0.2 mL/mouse (control group), orally intubated 100 mg ChV /kg (ChV group), orally intubated 100 µg/mL NIC in 2% saccharin (NIC group), and orally intubated NIC + ChV as in group 3 and 2 (NIC+ChV group). The dosing was daily for 4 weeks. Mice from all experimental groups were then inoculated intraperitoneally with viable tumor cells 2.5 × 106 (0.2 mL/mouse) in the fourth week, and the treatments were extended for another 2 weeks. The results have shown that NIC exposure significantly altered the serum levels of liver function indices, lipid profile, LDH, and ALP in the NIC-exposed group. NIC administration significantly increased hepatic inflammation, lipid peroxidation, and DNA damage-related biomarkers but reduced antioxidant enzyme activities. NIC exposure downregulated SOD1, SOD2, CAT, GPX1, and GPX2 but upregulated NF-κB hepatic gene expression. Notably, the presence of the EAC cells outside the liver was common in all mice groups. Liver tissue of the NIC-exposed group showed multifocal expansion of hepatic sinusoids by neoplastic cells. However, with no evidence of considerable infiltration of EAC cells inside the sinusoids or in periportal areas in the NIC + ChV groups. NIC significantly altered caspase-3, Bax, and BcL2 hepatic immune expression. Interestingly, ChV administration significantly mitigates NIC-induced alterations in hepatic function indices, lipid profile, and the mRNA expression of antioxidant and NF-κB genes and regulates the caspase-3, Bax, and BcL2 immunostaining. Finally, the in vivo protective outcomes of ChV against NIC-induced hepatic injury combined with EAC in female Swiss mice could suggest their helpful role for cancer patients who are directly or indirectly exposed to NIC daily.

Potential of Caffeic Acid and 10-Dehydrogingerdione as Lipid Regulators Relevant to Their Inhibitory Effect on miR-122 and ATP Citrate Lyase Activity in Diabetic Hyperlipidemic Rats.

The present study aimed to illustrate the hypolipemic effect of 10-Dehydrogengardione (10-DHG) or caffeic acid (CA) with reference to the role of microRNA-122 (miR-122) and ATP citrate lyase (ACLY) activity. Diabetic hyperlipidemia was induced in rats, and then randomly classified into three groups. The first one received only a CCT-diet for 6 weeks and was referred to as the positive control. The other two groups received 10-DHG (10 mg/kg/day) or CA (50 mg/kg/day), orally for 6 weeks along with a CCT-diet. Another group of normal rats was included, received a normal diet, and was referred to as the negative control. Either 10-DHG or CA significantly decreased MiR-122 expression and appeared more remarkable in the CA group by 15.5%. The 10-DHG greatly enhanced phosphorylated form of AMP activated protein kinase (p-AMPK) activity, more than CA by 1.18-fold, while the latter exerted more inhibitory effect on ACLY, and fatty acid synthase (FAS) activities compared with 10-DHG (p < 0.05). Both drugs significantly decreased hydroxy methyl glutaryl coenzyme A (HMG-COA) reductase activity, which appeared more remarkable in 10-DHG, and significantly decreased triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) along with a high density lipoprotein cholesterol (HDL-C) increase. The 10-DHG ameliorated the hepatic tissue lesions greatly, more than CA. The 10-DHG or CA significantly inhibited MiR-122, hepatic FAS, and ACLY levels along with p-AMPK activation. This subsequently led to reduced plasma TG, cholesterol levels, and blood glucose improvement and, indeed, may explain their mechanisms as hypolipemic agents.

Lycopene ameliorates hyperlipidemia via potentiation of AMP-activated protein kinase and inhibition of ATP-citrate lyase in diabetic hyperlipidemic rat model.

AIM: The present study aimed mainly to demonstrate the metabolic effects of lycopene (LYC) or atorvastatin (ATOR) in diabetic hyperlipidemic rat model. MAIN METHODS: Rats were randomly classified into four groups; the first was fed normal chow diet (NC) while the other three groups received streptozotocin (STZ) along with CCT-diet. The second group received no treatment (diabetic hyperlipidemic control, DHC), the third one received ATOR (50 mg/kg/day) while the fourth one received LYC (20 mg/kg/day). Serum and tissue samples were collected for biochemical and histological evaluations. KEY FINDINGS: DHC rats demonstrated significant hyperglycemia, dyslipidemia, increased hepatic fatty acid synthetase (FAS), malondialdehyde (MDA), tumor necrosis factor- alpha (TNF-α), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase and ATP citrate lyase (ACLY). However, hepatic reduced glutathione (GSH) and phosphorylated form of AMP-activated protein kinase (AMPK-P) activities showed significant decreases. ATOR or LYC administration induced hypoglycemic and hypolipidemic effects; decreased hepatic levels of MDA, TNF-α, HMG-CoA reductase, ACLY and FAS along with GSH and AMPK-P increases. Histopathological findings showed clear correlation with the biomarkers results. SIGNIFICANCE: LYC demonstrated favorable significant effects regarding the biomarkers studied as compared to ATOR and may be expressed as a potent therapeutic agent of natural origin for hyperlipidemia complications either alone or in combination with other hypolipidemic drugs.

Ellagic acid ameliorates high fructose-induced hyperuricemia and non-alcoholic fatty liver in Wistar rats: Focusing on the role of C1q/tumor necrosis factor-related protein-3 and ATP citrate lyase.

AIMS: High-fructose intake (HF) represents an inducible risk factor for non-alcoholic fatty liver disease (NAFLD). Present study aimed to illustrate the effect of HF diet (HFD) on the induction of NAFLD, hyperuricemia and role of ellagic acid as modulator. MAIN METHODS: Twenty-four adult male albino rats were randomly divided into four groups (6/each). The first group received normal chow diet only while the others received 60 % HFD for 4 weeks and subdivided later into 3 groups. The first and second groups received allopurinol and ellagic acid, respectively while the third group received HFD only for extra 4 weeks. KEY FINDINGS: Rats fed on HFD for 8 weeks displayed body weight gain, insulin resistance (IR), hyperglycemia, dyslipidemia, hyperuricemia with increased oxidative stress and hepatic lipogenic enzymes such as ATP citrate lyase (ACL), aldolase B, and fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SERBP-1c). C1q /tumor necrosis factor-related protein -3 (CTRP3), and phosphorylated AMP-activated protein kinase (p-AMPK) however showed significant decreases. Ellagic acid or allopurinol administration significantly decreased serum lipids, uric acid, glucose, insulin levels and hepatic contents of enzymes. Malondialdehyde (MDA), FAS, aldolase B, SERBP-1c, and xanthine oxidase (XO) hepatic contents showed significant decreases along with glutathione (GSH) increase as compared to fructose group where ellagic acid was more remarkable compared with allopurinol. SIGNIFICANCE: Our findings indicated that ellagic acid had alleviated HFD-induced hyperuricemia, its associated NAFLD pattern as mediated through activation of CTRP3 and inhibition of ACL activities in a pattern more remarkable than allopurinol.

Use of radiographic and histologic scores to evaluate cats with idiopathic megacolon grouped based on the duration of their clinical signs.

Since the duration of clinical signs could be used to identify cases of chronic constipation, in addition, prolonged duration is often associated with irreversible changes. Thus, the main objective of this study was to determine whether the duration of clinical signs of idiopathic megacolon in cats affected their diagnosis and prognosis after treatment. Medical records of cats that either had confirmed megacolon for an unknown cause (cat patients) or with normal bowels (control cats) were reviewed. Cat patients were grouped based on the duration of their clinical signs (constipation/obstipation) to cats <6 months and ≥6 months. For all feline patients, abdominal radiographs (for colonic indexes) and resected colon specimens (for histology) were assessed vs. control cats. Treatment applied to cat patients was also evaluated. Cat patients were older (p = 0.0138) and had a higher maximum colon diameter (MCD; mean 41.25 vs. 21.67 mm, p < 0.0001) and MCD/L5L ratio (1.77 vs. 0.98, p < 0.0001) than controls. Compared to cats with <6 months, cats ≥6 months showed a higher MCD (43.78 vs. 37.12 mm, p < 0.0001) and MCD/L5L ratio (1.98 vs. 1.67, p < 0.0001). Histologically, increased thickness of the smooth muscularis mucosa (54.1 vs. 22.33 µm, p < 0.05), and inner circular (743.65 vs. 482.67 µm, p < 0.05) and outer longitudinal (570.68 vs. 330.33 µm, p < 0.05) smooth muscular layers of the muscularis externa was noted only in cat patients with ≥6 months compared to controls. Similarly, fewer ganglion cells (0.93 vs. 2.87, p < 0.005) and more necrotized myocytes (2.25 vs. 0.07, p < 0.005) were observed in cats with ≥6 months. In contrast to <6 months, the majority of cats (94.4%) with ≥6 months duration did not show any response to medical treatment and therefore underwent surgery with favorable results. In conclusion, this study suggests that the duration of clinical signs should be considered in conjunction with maximal colon scores to evaluate cats for idiopathic megacolon and determine the level of treatment. Functional abnormalities of the colonic smooth muscles may be a possible cause of idiopathic megacolon in cats.

Fetal lesions of EHV-1 in equine.

EHV-1 infection is responsible for huge economic losses in equines due to abortion and neonatal mortality. In this study, we describe 4 cases of abortion and neonatal deaths from pregnant mares and a she-donkey from different localities in Egypt during the period from May 2015 to October 2017. Attempts were made to isolate and identify EHV-1, in addition to compare the different pathological lesions in various tissues of the necropsied cases. EHV-1 was successfully isolated from two aborted fetuses and one dead neonatal foal from mares, beside one aborted fetus from a she-donkey. The positive cases showed cytopathic effect on embryonated chicken eggs scattered on chorioallantoic membrane. Moreover, PCR was applied for the pock lesions and revealed positive results for EHV-1. Interstitial pneumonia, bronchopneumonia and necrosis of hepatic, myocardial, microcotyledonary tissues besides disseminated thrombi were the main encountered lesions. Intranuclear inclusion bodies were demonstrated in brain, liver, placenta and pulmonary tissues. Here, we describe EHV-1 induced brain lesions represented by degenerated neurons, vascular endotheliosis with intranuclear inclusion bodies in the aborted she-donkey fetus. Lesions were more sever in the aborted fetuses from mares than the one from the she-donkey. EHV-1 antigen was detected by immunohistochemistry staining.