Effectiveness of cannabidiol (CBD) on histopathological changes and gene expression in hepatocellular carcinoma (HCC) model in male rats: the role of Hedgehog (Hh) signaling pathway.

The third most prevalent malignancy to cause mortality is hepatocellular carcinoma (HCC). The Hedgehog (Hh) signaling pathway is activated by binding to the transmembrane receptor Patched-1 (PTCH-1), which depresses the transmembrane G protein-coupled receptor Smoothened (SMO). This study was performed to examine the preventative and therapeutic effects of cannabidiol in adult rats exposed to diethyl nitrosamine (DENA)-induced HCC.A total of 50 male rats were divided into five groups of 10 rats each. Group I was the control group. Group II received intraperitoneal (IP) injections of DENA for 14 weeks. Group III included rats that received cannabidiol (CBD) orally (3-30 mg/kg) for 2 weeks and DENA injections for 14 weeks. Group IV rats received oral CBD for 2 weeks before 14 weeks of DENA injections. Group V included rats that received CBD orally for 2 weeks after their last injection of DENA. Measurements were made for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and alpha fetoprotein (AFP). Following total RNA extraction, Smo, Hhip, Ptch-1, and Gli-1 expressions were measured using quantitative real-time polymerase chain reaction (qRT-PCR). A histopathological analysis of liver tissues was performed.The liver enzymes, oxidant-antioxidant state, morphological, and molecular parameters of the adult male rat model of DENA-induced HCC showed a beneficial improvement after CBD administration. In conclusion, by focusing on the Hh signaling system, administration of CBD showed a beneficial improvement in the liver enzymes, oxidant-antioxidant status, morphological, and molecular parameters in the DENA-induced HCC in adult male rats.

The potential protective and therapeutic effects of cannabidiol oil on experimental Leukemia induced by DMBA in male rats.

BACKGROUND: 7,12-Dimethylbenzanthracene (DMBA) is a member of the polycyclic aromatic hydrocarbon family. It is a member of the polycyclic aromatic hydrocarbon family. It is a mutagenic, carcinogenic, and immunosuppressor agent. Cannabidiol (CBD) is a phytocannabinoid. It has anticonvulsant, anti-inflammatory, anti-anxiety, antioxidant, and anti-cancer properties. The purpose of this study was to investigate the possible protective and therapeutic benefits of CBD oil in DMBA-induced leukemia in rats. METHOD: Experimental animals were divided into six groups of five rats each. Group 1 (normal control) included healthy rats. Group 2 included normal rats that received olive oil. Group 3 included normal rats that received CBD. Group 4 included the DMBA-induced leukemic group. Group 5 (prophylactic group) included rats that received CBD as a prophylaxis before IV injection with DMBA. Group 6 (treated group) included DMBA-induced leukemic rats that received CBD as treatment. Liver functions (total, direct and indirect bilirubin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), albumin, globulin, and albumin globulin ratio) were measured. Superoxide dismutase (SOD) and catalase (CAT) were also measured. Total RNA extraction followed by-real time qRT-PCR gene expression of LC3-II, Beclin, mTOR, and P62 was performed. Histopathological examination of liver and spleen tissues was performed. RESULTS: Administration of CBD in groups 5 and 6 resulted in a significant improvement of the levels of liver functions compared to the leukemic untreated rats. Also, the levels of catalase and SOD significantly increased after treatment with CBD compared to the leukemic group. After treatment with CBD in groups 5 and 6, there were downregulations in the expression of all studied genes compared to leukemic untreated rats. Treatment with CBD was more statistically effective than prophylactic use. CONCLUSION: Administration of CBD resulted in a significant improvement in the biochemical, antioxidant status, morphological, and molecular measures in DMBA-induced leukemia in adult male rats. The therapeutic use was more effective than the prophylactic one.

Prospective affirmative therapeutics of cannabidiol oil mitigates doxorubicin-induced abnormalities in kidney function, inflammation, and renal tissue changes.

Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection. The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V). The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results. As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems.

Fractionation and characterization of Cerastes cerastes cerastes snake venom and the antitumor action of its lethal and non-lethal fractions.

In the present study fractionation of the Cerastes cerastes cerastes snake venom by gel filtration on Sephadex G-75 gave 14 protein fractions. Phospholipase PLA2 activity is not uniformly correlated with the lethality to mice in regard to all venom fractions. F11 which is the richest in PLA2 activity is less toxic than F3, which contains a small amount of PLA2, and F12 is the lowest in lethality and PLA2 activity. Treatment of Ehrlich ascites-bearing mice with two i.p. injections of the most lethal fraction (F3) or a non-lethal fraction (F4) resulted in a significant antitumor activity demonstrated by an increase in the mean survival time of the animals (22.5 and 27.9 days) and in the tumor inhibition ratio of tumor growth (T/C% 139 and 172, respectively), compared to tumor-bearing controls. The cytotoxic activity of F3 and F4 against Ehrlich ascites carcinoma cells might be due to the presence of a cytotoxin rather than to the direct cytolytic effect of the PLA2 because the non-lethal F4 is free from PLA2. Treatment of Swiss albino mice with two i.p. injections of F3 or F4 at the adopted dose levels produced no detrimental side effects demonstrated by the insignificant changes in the tested serum and liver parameters. Treatment of the tumor-bearing mice with the same venom fractions significantly modulated all of the studied biochemical parameters in the serum and liver tissues, compared to normal controls.