L-carnitine and Ginkgo biloba Supplementation In Vivo Ameliorates HCD-Induced Steatohepatitis and Dyslipidemia by Regulating Hepatic Metabolism.

Treatment strategies for steatohepatitis are of special interest given the high prevalence of obesity and fatty liver disease worldwide. This study aimed to investigate the potential therapeutic mechanism of L-carnitine (LC) and Ginkgo biloba leaf extract (GB) supplementation in ameliorating the adverse effects of hyperlipidemia and hepatosteatosis induced by a high-cholesterol diet (HCD) in an animal model. The study involved 50 rats divided into five groups, including a control group, a group receiving only an HCD, and three groups receiving an HCD along with either LC (300 mg LC/kg bw), GB (100 mg GB/kg bw), or both. After eight weeks, various parameters related to lipid and glucose metabolism, antioxidant capacity, histopathology, immune reactivity, and liver ultrastructure were measured. LC + GB supplementation reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, insulin, HOMA-IR, alanine transaminase, and aspartate transaminase levels and increased high-density lipoprotein cholesterol levels compared with those in the HCD group. Additionally, treatment with both supplements improved antioxidant ability and reduced lipid peroxidation. The histological examination confirmed that the combination therapy reduced liver steatosis and fibrosis while also improving the appearance of cell organelles in the ultrastructural hepatocytes. Finally, the immunohistochemical analysis indicated that cotreatment with LC + GB upregulated the immune expression of GLP-1 and ß-Cat in liver sections that were similar to those of the control animals. Mono-treatment with LC or GB alone substantially but not completely protected the liver tissue, while the combined use of LC and GB may be more effective in treating liver damage caused by high cholesterol than either supplement alone by regulating hepatic oxidative stress and the protein expression of GLP-1 and ß-Cat.

Immunostimulatory and anti-inflammatory impact of Fragaria ananassa methanol extract in a rat model of cadmium chloride-induced pulmonary toxicity.

Cadmium is an extremely dangerous heavy metal that can lead to disastrous consequences in all organisms. Several natural remedies reduce the toxicities of experimentally generated metals in animals. Strawberry Fragaria ananassa contains several bioactive compounds that may mitigate heavy-metal toxicity. The study aim was to evaluate the ability of a strawberry fruit methanol extract (SE) to reduce Cd toxicity and to identify and quantify the active constituents of SE. Forty Wistar rats were classified into four groups: the control group- 1 ml saline IP; SE group- 100 mg of SE/kg rats orally; cadmium (Cd) group-2 mg CdCl2/kg body weight/IP daily; and treated group- SE given 1 hour before Cd administration. Administration of Cd induced several histopathological and immunohistochemical alterations in lung sections. Biochemical analysis of lung homogenates and mRNA levels of antioxidants and inflammatory cytokines indicated significant changes to the risk profile. SE administration significantly decreased the oxidative stress, inflammation, tissue damage, the mean area percentage of collagen fibers, and positive immuno-expressions of TNF-α and NF-κB induced by CdCl2. Moreover, the MDA, TNF-α, GM-CSF, and IL-1ß levels in Cd-exposed rat lung tissue were significantly lower in the SE-treated group than in the Cd-group. SE significantly augmented lung GSH, SOD, HO-1, GPx-2, and Nrf2 levels in Cd-exposed rats. SE mitigated Cd-caused oxidative stress and lung inflammation. Therefore, regularly consuming a strawberry-rich diet could benefit general health and help prevent and treat diseases.

Impact of Synthesized Indoloquinoline Analog to Isolates from Cryptolepis sanguinolenta on Tumor Growth Inhibition and Hepatotoxicity in Ehrlich Solid Tumor-Bearing Female Mice.

The study evaluated the antitumor efficacy of APAN, "synthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta", versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect against etoposide-triggered hepatic disorders. APAN showed an ameliorative activity against Ehrlich solid tumor and hepatic toxicity, and the greatest improvement was found in the combined treatment of APAN with ETO. The results indicated that EST altered the levels of tumor markers (AFP, CEA, and anti-dsDNA) and liver biomarker function (ALT, AST, ALP, ALB, and T. protein). Furthermore, EST elevated CD68 and anti-survivin proteins immuno-expressions in the solid tumor and liver tissue. Molecular docking studies were demonstrated to investigate their affinity for both TNF-α and topoisomerase II as target proteins, as etoposide is based on the inhibition of topoisomerase II, and TNF-α is quite highly expressed in the solid tumor and liver tissues of EST-bearing animals, which prompted the authors' interest to explore APAN affinity to its binding site. Treatment of mice bearing EST with APAN and ETO nearly regularized serum levels of the altered parameters and ameliorated the impact of EST on the tissue structure of the liver better than that by treatment with each of them separately.

Gum Acacia attenuates cisplatin toxic effect spermatogenesis dysfunction and infertility in rats.

This study aimed to investigate the potential benefits Gum Arabic/Acacia senegal (GA) in mitigating the harmful effects of cisplatin (CP) on spermatogenesis and testicular health in male adult rats. A total of forty albino rats were used in the study and divided into four groups; control, GA, CP, and Co-treated group, which received both CP and GA concurrently. The results revealed that CP caused a significant increase in oxidative stress and a decrease in antioxidant activities (CAT, SOD, and GSH), which disturbed the testicular machinery. This caused significant histological and ultrastructural damage to the testicular structure, including atrophied seminiferous tubules with severely reduced germinal epithelium. Additionally, CP caused a decrease in reproductive hormones (testosterone and LH), a decline in nucleic proliferation PCNA immunoexpression, and an increase in cytoplasmic apoptotic Caspase-3 protein expression in testicular tissue, when compared to the control and GA groups. Moreover, the CP treatment impaired spermatogenesis and decreased sperm number and motility with abnormal morphology. However, co-administration of GA with CP mitigated the dysfunction in spermatogenesis and reversed testicular damage caused by CP through significantly (P < 0.01) reducing oxidative stress (MDA) and increasing the activities of CAT, SOD, and GSH. Additionally, co-administration of GA elevated the levels of testosterone and luteinizing hormone in blood sera, significantly (P < 0.01) improved the histometric measurements of seminiferous tubules diameter, their epithelial height, Johnsen's score of spermatogenesis, 4-level histological grading scale Cosentino's score, immunohistochemical expression of nucleic PCNA, and cytoplasmic Caspase-3 proteins. Furthermore, TEM examination confirmed the synergistic effect of GA in restoring the germinal epithelial cells ultrastructure, the elongated and transverse sections of spermatozoa in the lumen, and the interstitial tissue. All of these effects resulted in a significant improvement in sperm quality in the Co-treated animals compared with the CP group, as well as, a significant decline in the morphological abnormalities of sperm in Co-treated rats compared to those in the CP group. GA is a valuable agent for ameliorating chemotherapy-related infertility.

The Effect of Neonicotinoids Exposure on Oreochromis niloticus Histopathological Alterations and Genotoxicity.

This study aimed to examine the side effects of selected neonicotinoids (Acetamiprid, Aceta, and Imidacloprid, Imid) on Oreochromis niloticus juveniles. The acute toxicity, Probit method, revealed an LC50 of 195.81 and 150.76 ppm for Aceta/96 h and Imid/72 h respectively. The fish were divided into three groups that were exposed, for 21 days (n = 5/replicate), to 1/10 of the LC50 of either neonicotinoids, however, the third was an unexposed control group. Results of erythrocytic micronucleus (MN), and nuclear abnormalities (NA) showed that Aceta and Imid exposure caused a significant (p < 0.05) increase in MN by ~ 2.2 and ~ 10 folds, respectively relative to control. NAs occurred at the order of kidney-shaped > budding > binucleated in Aceta, however, budding > binucleated > kidney-shaped was noticed in the Imid group. Histopathological changes in gills, liver, and muscles were observed significantly in both exposed groups with more severity in the Imid group. Collectively, Aceta and Imid have potential genotoxicity and histopathological alterations in O. niloticus.

OMA1520 and OMA1774, novel 1,2,4-triazole bearing analogs of combretastatin A-4, inhibit hepatocellular carcinoma: Histological and immunohistochemical studies.

Combretastatin A-4 (CA-4) received significant interest as a potential anticancer agent in recent years. Several CA-4 analogs were synthesized and investigated to enhance the activity or solve the in vivo decreased activity of CA-4. AIM: The present study aims to investigate the chemotherapeutic and the antiproliferative effects of the mono and the dual therapy of the newly synthesized CA-4 analogs OMA1520 and OMA1774 against hepatocellularcarcinoma (HCC) induced in male adult rats by N-methylnitrosourea (MNU). METHODS: 50 male rats were divided into 5 groups of 10 animals in each group. Group I: normal healthy control; group II: MNU treated group, group III: MNU animals treated by OMA1520, group IV: MNU animals treated by OMA1774, and group V: MNU animals treated by both OMA1520 and OMA1774. The rats were assessed for liver cancer progression or inhibition by evaluating the histopathological, immunohistochemical, biochemical, and antioxidant enzyme status. RESULTS: The present work indicated that OMA1520 and OMA1774 possessed substantial chemotherapeutic efficiency against HCC. The histological and immunohistochemical examinations of liver tissues confirmed the biochemical sera data. Also, they diminished the cytotoxic effects of MNU and restored the normal histological hepatic architecture. Both analogs restored the normal levels of liver enzymes and functions and revealed potential antioxidant effects. OMA1520 and OMA1774 reduced the inflammatory and tumor markers' elevated expressions in serum. CONCLUSION: Substantial evidence in our results suggests that both CA-4 analogs could be possible alternative anticancer agents, and their co-administration provides a synergistic activity.