Maternal and Fetal Hepatic Injury in Gestational Diabetic Rats: Protective Role of Cinnamaldehyde and Ellagic Acid

Abstract

Objective: This study aims to determine the protective effect of cinnamaldehyde (Ci) and ellagic acid (EA) on maternal and fetal hepatic injury caused by fatty-sucrosed-diet/streptozotocin (FSD/STZ)-rat model of gestational diabetes (GD).Methods: Female Wistar rats were allocated into four groups. Group I fed with a normal diet, while Groups II, III, and IV feds with FSD for 8 weeks (five pre-gestational and three gestational). One week before mating onward, Group III and IV administered daily oral dose of 20 mg/kg Ci or 50 mg/kg EA, respectively. At the 7th day of gestation, FSD-fed groups injected intraperitoneally with STZ (25 mg/kg b.wt.) to induce GD mellitus. At the end of gestation, maternal and fetal blood, pancreas and liver samples were taken for the subsequent analysis.Results: Ci and EA potentially protect from the elevated glucose, triglycerides, total cholesterols, liver transaminases, and the depleted serum insulin, high-density lipoprotein-cholesterol, total proteins and albumin of GD-rats. As well, tested agents alleviated the altered fetal glucose and insulin levels. Alongside, Ci and EA reduced the maternal and fetal liver lipid peroxidation and increased their total thiols and total peroxidases. Furthermore, Ci and EA kept the normal intact of maternal and fetal pancreatic islets and preserve their livers away from the pathological changes observed in GD group that included fatty depositions, inflammation, hepatocytic necrosis and fibrosis, congested veins, diminutive storable glycogen and proteins, and the numerous proliferating cell nuclear antigen nuclei.Conclusion: Ci and EA have potent hepatoprotective effects through their insulin-sensitizing action and activating the antioxidant defenses.

Potential roles of ellagic acid on metabolic variables in diabetes mellitus: A systematic review

“…In addition, ellagic acid treatment resulted in a significant increase in plasma levels of insulin and C‐peptide as well the activities of glucose‐6‐phosphatase and fructose‐1, 6‐bisphosphatase and glycogen in the liver 16 . Similarly, Abdel‐Moneim et al reported that type 1 diabetic rat models treated with 50 mg/kg ellagic acid showed improved FBS and OGTT and a significant increase fasting insulin levels 27,28 . Both Al‐Tamimi et al and Altındag et al observed a significant decrease in serum levels of FBS and a significant increase in fasting insulin levels after supplementation with 50 mg/kg of ellagic acid in type 1 diabetic rat models 30,32 .…”

“…In addition, Altındag et al found that administration of 50 mg/kg ellagic acid led to elevated MDA and increases in GSH and CAT pancreatic levels in type 1 diabetic rat models 33 . Similarly, Abdul‐hamid et al indicated that 50 mg/kg ellagic acid led to a reduction in MDA and increased total thiols and total peroxidase hepatic levels in type 1 diabetic rat models 27 . Likewise, Abdel‐Moneim et al reported a decrease in MDA and NO, improved activity of CAT enzymes and reduction in TNF‐α serum levels after supplementation with 50 mg/kg ellagic acid in type 1 diabetic rat models 28 .…”

“…The results of this systematic review indicate that ellagic acid administration has a potentially useful effect on improving FBS, 14–19,22–30,32–36 OGTT, 22,27,28 insulin, 14,18,22,24,27–30,32,33,35,36 HbA1c, 15,18,19,21,23,24,34,35 and HOMA‐IR 19,22,25,35,36 in both animal and human models as well as AUC, 22 number, size and function of beta cells, 24,29,33 serum levels of C‐peptide, 16 and glycogen in liver and muscle 16,27 in animal models.…”

“…Moreover, Ahad et al observed that 16 weeks of intervention with 20–50 mg/kg ellagic acid in type 1 diabetic rat models led to a decrease in serum levels of = TG, TC, LDL‐C, VLDL‐C and FFA, and an increase in HDL‐C 19 . At higher doses, Abdel‐Moneim et al and Abdul‐hamid showed that in type 1 diabetic rat models treated with 50 mg/kg ellagic acid showed reduced serum levels of TG and TC and a significant increase in HDL‐C levels in type 1 diabetic rat models 27,28 . Similarly, Al‐Tamimi et al and Altındag et al found that administration of 50 mg/kg of ellagic acid in type 1 diabetic rat models for 4–12 weeks led to decreases in TG, TC, LDL‐c and FFA 30,32 .…”

Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress

“…Thickening of the interhemal membranes -++ -+ hyperglycemia and hyperinsulinemia. Concisely, maternal hyperglycemia resulted in a transplacental flux of glucose down the concentration gradient into the fetal circulation, and according to Pedersen's hypothesis, this fetal hyperglycemia stimulated the fetal pancreatic β-cell hyperplasia to increase the insulin secretion in order to achieve normoglycemia [87,88]. Due to the short pregnancy period of rats, and as Ci is effective for a treatment duration of 21 to 60 days [25], Ci was given one week prior to mating.…”