Objectives A large amount of fructose is metabolized in the liver and causes hepatic functional damage. Δ9‐tetrahydrocannabinol (THC) is known as a therapeutic agent for clinical and experimental applications. The study aims to investigate the effects of THC treatment on inflammation, lipid profiles and oxidative stress in rat liver with hyperinsulinemia. Methods Sprague‐Dawley rats were divided into groups: control, fructose (10% fructose in drinking water for 12 weeks), THC (1.5 mg/kg/day for the last 4 weeks, intraperitoneally) and fructose+THC groups. Biochemical parameters were measured spectrophotometrically. ELISA method was used for insulin measurement. Apoptosis and inflammation markers were detected by the streptavidin‐biotin peroxidase method. Key findings The consumptions of food and fluid are inversely proportional to fructose and non‐fructose groups. Insulin levels were the highest in fructose group. The reduced glutathione‐S‐transferase level significantly increased in fructose + THC group compared with fructose group. Total cholesterol level in the fructose + THC group was higher than the fructose group. Caspase‐3 and NF‐κβ immunopositive cell numbers increased in fructose + THC rats compared with fructose group. The number of IL‐6 immunopositive cell decreased in fructose + THC group compared with fructose group. Conclusions According to the result, long‐term and low‐dose THC administration may reduce hyperinsulinemia and inflammation in rats to some extent.

Diabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic β cell dysfunction. Pancreatic β cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance. Δ9‐Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent. Our aim was to evaluate the effects of THC in the diabetic kidney. We analyzed macromolecular damage biomarkers as protein carbonyl (PCO), lipid hydroperoxide (LHP), malondialdehyde (MDA), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and antioxidant defense system biomarkers as thiol fractions (T‐SH, NP‐SH, P‐SH) and Cu/Zn‐superoxide dismutase activity for the antioxidative effects of THC. Furthermore, mRNA expression of Krüppel‐like factor‐4, secreted immunopositive cell number changes of interleukin‐6, nuclear factor κβ (NF‐κβ), and peroxisome proliferator‐activated receptor‐γ and tumor necrosis factor α (TNF‐α) levels were analyzed for the immunomodulatory activity of THC. Diabetic rats showed significantly increased levels of PCO, LHP, MDA, and 8‐OHdG when compared with controls (P < 0.05 for each parameter). THC significantly reduced the elevated levels of PCO and 8‐OHdG (P < 0.05 for both parameters) and also LHP and MDA levels were insignificantly reduced by THC. Also, thiol fractions insignificantly increased in THC administered diabetic kidney when compared with diabetic rats. The NF‐κβ cell number significantly decreased in the diabetic rats treated with THC compared with the diabetic group. According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.

According to our findings, we suggest that silibin treatment after EAT cells inoculation has more effective than concurrently EAT and silibin treatment.

The aim of the study is to clarify the effect of ghrelin treatment on the messenger RNA (mRNA) expression of the cannabinoid receptor 1 (Cnr1/CB1) and glucagon‐like peptide 1 receptor (Glp1r/GLP‐1R) as well as microRNAs (miR)‐122 and miR‐33a in the liver of rats with type 2 diabetes mellitus (T2DM). Adult Sprague‐Dawley rats were divided into three groups: control (n = 7), T2DM (n = 7), and treatment (n = 7). Control animals received tap water. T2DM was induced by feeding 10% fructose in drinking water for 2 weeks followed by a single injection of streptozotocin (40 mg/kg, intraperitoneally [IP]). In the treatment group, diabetic rats were injected ghrelin (25 μg/kg, IP) for 14 days. Serum lipid profiles were evaluated, and mRNA expression levels of Cnr1 and Glp1r in the liver were detected using quantitative real‐time polymerase chain reaction (RT‐qPCR). In addition, miR‐122 and miR‐33a levels were measured using RT‐qPCR. Serum triglycerides, low‐density lipoprotein cholesterol, and very‐low‐density lipoprotein cholesterol significantly increased in the T2DM group compared with control rats but ghrelin treatment showed no effect on serum lipid levels. The mRNA expression levels of Cnr1 and Glp1r decreased in the T2DM group compared with the control group. These reductions were significantly increased in the T2DM group treated with ghrelin. Furthermore, the increase in miR‐33a expression level was reduced in the treatment group compared to rats with T2DM. Our findings suggested that ghrelin treatment may alter the mRNA expression levels of CB1 and GLP‐1R in the liver of rats with T2DM. The mRNA levels of Cnr1 and Glp1r may inversely correlate with the expression level of miR‐33a but not miR‐122.

Objectives This study was designed to clarify the effects of ghrelin on myocardial and aortic tissues in insulin-resistant rats. Methods Sprague-Dawley rats were divided into the following groups: control (Group 1), insulin resistance (IR, Group 2), ghrelin (Group 3) and IR+Ghrelin (Group 4) groups. Levels of HOMA-IR, fibronectin, hydroxyproline, collagen-1, collagen-3, matrix metalloproteinase-3, and matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1, and oxidative stress parameters as protein carbonyl (PCO), lipid hydroperoxides (LHPs), malondialdehyde, total thiol were determined in myocardial tissue. Expressions of IL-6, NF-κB and TNF-α mRNAs were detected by RT-qPCR. Aorta tissue was stained Masson trichrome. Key findings The HOMA-IR level decreased in the IR+Ghrelin group compared with the IR group (P &lt; 0.001). The PCO and LHP concentrations were higher in the IR group compared with control rats (P &lt; 0.05). The PCO level was reduced by ghrelin in the IR+Ghrelin group compared with the IR group (P &lt; 0.001). Ghrelin treatment reduced the mRNA expression levels of IL-6, NF-κB and TNF-α in the IR+Ghrelin group compared with the IR group (P &lt; 0.001). There was no difference among the groups in the histology of aortic tissue. Conclusions Ghrelin, a regulator of appetite and energy homeostasis, may be effective in regulating oxidative stress and the inflammatory response when impaired by IR. Therefore, ghrelin may reduce the risks of myocardial dysfunction in IR.