Abnormalities in insulin hormone levels leads to a hyperglycemic condition of diabetic mellitus. Hyperglycemia seriously induces organ and system destructions. The excessive accumulation of collagen fiber deposits occurs in inflammatory and reorganization processes of chronic liver diseases in type I insulin‑dependent diabetes. Regarding the research objective, glabridin (GLB), an active compound of licorice, was used as a daily supplement (40 mg/kg) in order to decrease hepatocyte destruction and collagen deposition in liver tissue of diabetic animals induced by streptozotocin. A total of 40 were randomly allocated to five groups (each, n=10), control, control treated with GLB (GLB), diabetic rats (DM) injected with single dose of streptozotocin (60 mg/kg) to induce a diabetic condition, diabetic rats receiving GLB (DM+GLB; 40 mg/kg) and diabetic rats treated with glibenclamide (DM+GL; 4 mg/kg). Characteristic histopathological changes in liver cells and tissues of rats were determined by Masson's trichrome staining and transmission electron microscopy (TEM). Western blotting was used to detect the expression of the key markers, collagen type I and fibronectin proteins. The histological investigation of liver tissue of the DM group revealed that the collagen fiber deposition was increased in the periportal, pericentral and perisinusoidal spaces compared with controls. Hepatocytes appeared as small and fragmented cells in TEM examination. Collagenization of the perisinusoidal space was recently demonstrated to represent a new aspect of the microvascular abnormalities and liver fibrosis. Healthy hepatocytes with round nucleus were observed following supplementation of glabridin. In addition, collagen fiber deposition was reduced in the area adjacent to the perisinusoidal space. The expression of collagen type I and fibronectin decreased strongly following glabridin supplementation in DM+GLB rats compared with DM rats, indicating that the hepatic tissue reorganization regained its normal morphology. These findings suggest that it may be beneficial to examine the role of glabridin as a therapeutic agent in diabetes treatment in future research.

Calloselasma rhodostoma (Malayan pit viper) is a medically important snake species that is widely distributed across Southeast Asia. Systemic coagulopathy causing severe haemorrhage and local tissue injury is commonly observed following C. rhodostoma envenoming. However, nephrotoxicity and congestive heart failure were previously reported in a patient who had a long length of hospital stay. In this study, we determined the effect of C. rhodostoma envenoming on cardiovascular disturbances and the associated morphological changes in the liver, heart and kidneys using animal models. We also evaluated the efficacy of Hemato polyvalent antivenom (HPAV; Queen Saovabha Memorial Institute (QSMI) of the Thai Red Cross Society, Thailand) in neutralising the histopathological effects of C. rhodostoma venom. The intravenous (i.v.) administration of C. rhodostoma venom (1000 µg/kg) caused a rapid decrease in mean arterial pressure (MAP) followed by complete cardiac collapse in anaesthetized rats. Moreover, the intraperitoneal (i.p.) administration of C. rhodostoma venom (11.1 mg/kg; 3 × LD₅₀) for 24 h caused cellular lesions in the liver and heart tissues. C. rhodostoma venom also induced nephrotoxicity, as indicated by the presence of tubular injury, interstitial vascular congestion and inflammatory infiltration in the whole area of the kidney. The administration of HPAV, at manufacturer-recommended doses, 15 min prior to or after the addition of C. rhodostoma venom reduced the extent of the morphological changes in the liver, heart and kidneys. This study found that experimental C. rhodostoma envenoming induced cardiovascular disturbances, hepatotoxicity and nephrotoxicity. We also highlighted the potential broad utility of HPAV to neutralise the histopathological effects of C. rhodostoma venom. The early delivery of antivenom appears capable of preventing envenoming outcomes.

The brain is a vital organ that requires a constant blood supply. Stroke occurs when the blood supply to specific parts of the brain is reduced; diabetes is an autonomous risk factor for stroke. The present study aimed to investigate the potential vascular protective effect of gymnemic acid (GM) by assessing the morphological changes of microvasculature, along with VEGFA and angiopoietin‑1 (Ang‑1) protein expression in the brains of diabetic rats. Rats were divided into five groups, including control, gymnemic control rats (CGM), rats that were rendered diabetic by single injection of 60 mg/kg streptozotocin (STZ), diabetic rats treated with 400 mg/kg GM (STZ + GM) and diabetic rats treated with 4 mg/kg glibenclamide (GL; STZ + GL). After 8 weeks, brain tissues were collected to examine the three‑dimensional morphology of the anterior cerebral arteries by vascular corrosion casting. Western blotting was performed to determine VEGFA and Ang‑1 expression. Cerebral arteries, arterioles and capillaries were depicted the diameter, thickness and collagen accumulation of the wall, and the results demonstrated narrow diameters, thickened walls and collagen accumulation in the STZ group. After receiving GM, the histopathological changes were similar to that of the control group. Through vascular corrosion casting and microscopy, signs of vessel restoration and improvement were exhibited by increased diameters, and healthy and nourished arterioles and capillaries following treatment with GM. Furthermore, VEGF expression and Ang‑1 secretion decreased in the STZ + GM group compared with STZ rats. The results of the present study revealed that GM treatment decreased blood vessel damage in the brain, suggesting that it may be used as a therapeutic target for the treatment of diabetes.

An understanding of snake venom pharmacokinetics is essential for determining clinical outcomes of envenoming and developing therapeutic approaches to the treatment of envenoming, especially regarding the timing and optimal dosage of antivenom administration. Daboia siamensis (Eastern Russell’s viper) envenoming causes systemic coagulopathy and severe hemorrhage including acute kidney injury. These toxic outcomes can be diminished by the administration of high quantities of Russell’s viper antivenom. This study aimed to determine the correlation between the clinical profiles of D. siamensis envenomed patients and experimental data by measuring plasma venom concentration and conducting histopathological analyses of heart, kidney, and liver tissues in rats 6 h after experimental D. siamensis envenomation. Intramuscular (i.m.) administration of D. siamensis venom to anesthetized rats (200 µg/kg) resulted in a rapid absorption of venom which reached a peak concentration at 60 min before declining and then plateauing. Urine samples detected 209.3 ± 21.6 ng/mL of D. siamensis venom following i.m. administration at 6 h. Histopathological studies showed morphological changes in heart, kidney, and liver tissues following 3 h experimental envenoming and exhibited a higher degree of severity at 6 h. A retrospective study of the clinical profile and laboratory examination of Russell’s viper envenomed patients in Central Thailand was also evaluated, showing that systemic coagulopathy and local effects were commonly observed in the early stage of D. siamensis envenoming. An abnormal increase in creatinine levels was found in 13.6% of the population. Early administration of specific antivenom within 1–2 h following envenoming is highly recommended to prevent life-threatening outcomes such as severe coagulation and acute kidney injury.

Clinical symptoms of monocled cobra (Naja kaouthia) envenoming include the paralysis of extraocular muscles, local tissue necrosis and death through respiratory failure. These neurotoxic outcomes are mainly due to the inhibitory action of postsynaptic neurotoxins to nicotinic acetylcholine receptors. However, injuries involving respiratory muscles have rarely been investigated. In this study, we determined the effect of N. kaouthia envenoming on morphological changes in the rat diaphragm. The efficacy of cobra monovalent antivenom in neutralising the histopathological effects of N. kaouthia venom was also evaluated. The intramuscular (i.m.) administration of N. kaouthia venom (2 mg/kg) caused skeletal muscle fibre atrophy and ruptures of myofibrils shown via a light microscope study. Transmission electron microscopy (TEM) revealed the zig-zagging of the Z-band, mitochondrial damages and degeneration of the synaptic fold of the neuromuscular junction following experimental cobra envenoming for 4 h. Intravenous administration of cobra antivenom at manufacturer-recommended doses diminished histopathological changes in the diaphragm following the administration of cobra venom. The expression of NF-kB and MuRF1 in the experimentally N. kaouthia-envenomed diaphragm indicated inflammation and tissue atrophy in the immunofluorescence analysis, respectively. In this study, we found that there were respiratory muscle injuries following N. kaouthia envenoming. The early administration of monovalent N. kaouthia antivenom is capable of neutralising neurotoxic outcomes following cobra envenoming.