Serological and Histological Evaluation of the Effect of Honeybee Venom on Pancreas and Liver in Diabetic Mice.

Natural toxins have been traditionally used to trigger several diseases among which bee venom (HBV) is of great importance. The present study aimed to investigate the therapeutic effects of honeybee venom (HBV) on alloxan and glucose fluid-induced Type 2 diabetes mellitus (T2DM). Therefore, a total of 20 adult laboratory male mice (Mus musculus) were selected, acclimated, and divided into four equal groups (n=5). Initially, 15 mice were fasted for 12 hrs and injected with alloxan at a single dose of 150 mg/kg of body weight. The animals were exposed to drinking glucose fluid in the morning for 4 days. Then, the blood glucose was measured. The studied animals having blood glucose of ≤200 mg/dl were considered non-diabetic and re-subjected to injecting alloxan (150 mg/kg body weight) and drinking glucose fluid for another 4 days. Four groups of mice population included, Group 1: non-diabetic and untreated with HBV, Group 2: diabetic and received no HBV as the potential therapeutic agent, Group 3: diabetic and received a low level of HBV at a dose of 0.5 mg/kg, Group 4: diabetic and received a high level of HBV at a dose of 1 mg/kg. At the end of the 35-day testing period, blood samples were tested to determine the levels of insulin, glucose, and lipid profiles [cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)] using Sandwich ELISA kits. The results indicated a significant increase in blood glucose in the diabetic group compared to that of the control one, while both concentrations of HBV significantly reduced the level of blood glucose compared to that of the diabetic group. Furthermore, the level of insulin was significantly decreased in the diabetic group compared to that of the controls, while HBV significantly increased the level of insulin compared to that of the diabetic group. Moreover, the diabetic mice demonstrated a significant increase in the concentration of cholesterol and TG compared to that of control mice which were significantly reversed in response to HBV treatment. The level of HDL was significantly decreased in the diabetic group compared to that of the control group which was modulated by treatment, while no significant differences were seen between all the studied groups regarding the level of LDL. Histological examination of diabetic mice revealed a significant alteration in acinar cells and destruction of ß-cells of pancreatic sections with marked lacerations in the liver extended to all structures of the organ. The present study concluded that HBV could be a potential therapeutic agent to prevent and manage diabetes and its complication.

Metformin and Bee Venom: a Comparative Detection of Histological Alteration of the Pancreas and Systemic Inflammatory Markers in Diabetic Mice.

Metformin is the approved medication for managing global health issues concerning type 2 diabetes mellitus (T2DM). Using natural bioactive compounds as an alternative therapy is crucial to managing several metabolic diseases. Therefore, due to recent limited studies that detected the role of bee venom (BV) in improving diabetic conditions in Iraq, the current study was designed to identify the potential therapeutic role of BV and metformin in diabetic mice. Twenty male mice (Balb/c) aged about 60 days with an average weight of 26.55±2.70 g were randomly divided into four groups (n=5). The animals were placed in plastic cages for acclimatization for one week of access to food and water ad libitum. Overnight fasting was applied to 15 mice which were then injected with 95 mg/kg body weight of prepared alloxan. The mice were supplemented with glucose fluid for 3 days. On day 4, the blood was collected from the tail to measure the circulating glucose level. When blood glucose levels exceed 200 mg/dl, the animals are considered diabetic. After induction of diabetes, the animals were divided as follows: Control group: included five mice that were not subjected to diabetes induction; the animals in this group: did not receive any medications. Diabetic group: including five mice confirmed with diabetes without receiving any treatments. Metformin group: including five diabetic mice exposed to a single oral dose of 150 mg/kg of metformin for 30 days. Bee Venom group: including five diabetic mice exposed to a single intraperitoneal dose of 1 mg/kg Bee Venom for 30 days. After 30 days of treatment, blood was drained, and serum was obtained to detect the levels of glucose, insulin, TNFα, IL6, and IL10 by using precise enzyme-linked immunosorbent assay (ELIZA) kits. Also, the pancreas was collected from all mice for histopathological investigation. The result displayed significantly elevated glucose concentration in diabetic mice, while metformin and BV significantly reversed these increases. A significant decline in insulin concentration was seen in diabetic mice, whereas metformin and BV significantly enhanced this reduction in insulin concentration. Furthermore, mice treated with alloxan exhibited remarkable increases in TNFα and IL6 compared to control mice, while supplemented metformin and BV significantly reduced these high concentrations. Moreover, the level of IL10 markedly declined in diabetic mice, which was reversed significantly in response to metformin and BV. Histological detection of the pancreas in diabetic mice showed significant changes in the shape and size of islets associated with the arrangement and number of beta cells with a reduction of islets covering connective tissue. Metformin slightly restored these alterations; however, significant and remarkable restoring of histological changing was promoted by BV. Thus, BV could be a potential agent for managing metabolic disorders including diabetes.