Potential Nephroprotective Effect of Dorsomorphin Homolog 1 (DMH1) in a rat model of diabetic nephropathy.

OBJECTIVE: Diabetic nephropathy (DN) represents the most common cause of end-stage renal disease. On the other hand, Bone Morphogenetic Protein signaling pathway (BMP/Smad) is one of the most interesting prophylactic targets, since inhibition of this pathway may preserve kidney functions. Therefore, a BMP pharmacological inhibitor, Dorsomorphin Homolog 1 (DMH1) was used to assess the potential nephroprotective effect in an animal model of DN. MATERIALS AND METHODS: STZ-induced diabetic rat was the selected model to assess the nephroprotective effect of DMH1(5 mg/kg) for eight weeks. Rats were divided into normal control (C=10), diabetic control (DC=10), diabetic+vehicle (DV=10) and diabetic DMH1-treated rats (DT=10). Fasting blood glucose (FBG) level was measured on a weekly basis. Then, glycated hemoglobin (HbA1c), serum Creatinine (sCr), Cystatin-C (Cys-C) and Blood Urea Nitrogen (BUN) were measured by the end of the experiment. Furthermore, Tumor Necrosis Factor (TNF-α), Interleukin-6 (IL-6) and Malondialdehyde (MDA) levels were determined in kidney tissues. The histopathological study was also performed using Hematoxylin and Eosin (H&E), Periodic acid Schiff (PAS) and Masson's trichrome stains. RESULTS: DMH1 treatment has significantly reduced HbA1c along with sCr, Cys-C and BUN vs. the diabetic non-treated groups (p < 0.001). Furthermore, TNF-α, IL-6 and MDA levels were also significantly decreased in the DT group compared to the diabetic non-treated groups (p < 0.001). This improvement was further confirmed and found in correspondence with histopathological findings. CONCLUSIONS: The present findings revealed a nephroprotective activity of DMH1 against STZ-induced DN in rats. DMH1 also showed anti-inflammatory and antioxidant activities, which may explain part of the nephroprotective mechanism. This can shed light on the importance of DMH1 and BMP/Smad pathway for further experimental studies.

The chemosensitizing effect of aqueous extract of sweet fennel on cisplatin treated HeLa cells.

BACKGROUND: Cisplatin is an important chemotherapeutic agent that is widely used in treatment of several malignancies, but its side effects on normal tissues and organs limit its use. The aim of this study was to evaluate the effect of aqueous extract of sweet fennel alone and in combination with cisplatin on human cervical cancer adenocarcinoma cell line (HeLa cells) searching for an effective, inexpensive therapy with minimal side effects. MATERIALS AND METHODS: HeLa cell line was used to study the cytotoxic effect of different concentrations of the aqueous extract of sweet fennel alone and in combination with 50 µg/ml cisplatin. Quantitative measure of drug interaction was quantified by the combination index. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) were used to analyze the sweet fennel decoction. MTT assay was used to examine cell viability percentage. Electron microscopy was applied to study the ultrastructure of the cells. RESULTS: The phenyl propanoids (23%) and phenols (12%) constituted the highest percentage of the aqueous extract. Increasing the concentration of sweet fennel from 50 µg/ml to 80 µg/ml, decreased the percentage of the cell viability of HeLa cells from 86.74% to 78.28%, respectively. Further decrease to 11.31% was demonstrated when 50 µg/ml of fennel was combined with 50 µg/ml cisplatin (additive effect). In addition to the signs of apoptosis observed in HeLa cells at 50 µg/ml of fennel, disruption of both nuclear and cytoplasmic membranes and presence of autophagolysosomes were noticed at a dose of 80 µg/ml. Combination of 50 µg/ml of cisplatin with 60, 70, and 80 µg/ml of sweet fennel revealed no significant difference in comparison to cisplatin alone. The combination with 50 µg/ml of sweet fennel revealed marked vacuolization of the cytoplasm, fragmentation of the nucleus, and complete disruption of nuclear membrane. CONCLUSIOn: Combination of cisplatin and the 50 µg/ml of the fennel could enhance cervical cancer growth inhibition. This combination could be effective in lowering the dose of single or repeated cumulative courses of cisplatin and hence decreases its hazardous side effects. In vivo studies and the evaluation of different combination doses of cisplatin and sweet fennel are recommended.

The beneficial roles of insulin and parathyroid hormones in the treatment of experimentally induced diabetic osteoporosis in female rats: bone mineral density, morphometric and histological studies.

BACKGROUND: Diabetes mellitus (DM) and osteoporosis are two frequent medical conditions with an increasing prevalence in elderly people and are responsible for large number of incurable fractures. This study is designed experimentally in female rats in order to determine whether combined treatment of insulin and parathyroid hormone (PTH) enhances the reversibility of the osteoporotic changes that occurred in streptozotocin (STZ)-induced DM. MATERIALS AND METHODS: In this study, 30 adult female rats aged 3 months were used, they were randomly divided into: control group (6 rats) and diabetes group (24 rats), in which experimental DM was induced by i.p. injection of a single dose of STZ (60 mg/kg/body weight). Diabetic group was further divided into four subgroups (6 rats each): non-treated diabetic, insulin-treated (8-12 units s.c./day of Humalin U-40), PTH-treated (6.0 µg s.c./kg/day) and combined insulin and PTH-treated subgroups. All tested groups were assessed for body weight, food and water consumptions. RESULTS: At the end of the experimental period, the bone mineral density (BMD) was measured for all rats of different groups; then the rats were sacrificed and blood samples were collected for measuring glucose, alkaline phosphatase and osteocalcin levels. Right femora were dissected out and subjected to measurement of diameter of neck and shaft, length of shaft, and weight. Then the femora specimens were processed and stained with haematoxylin and eosin for histological study. The results showed that there was a statistically significant, decrease in BMD, increase in the level of alkaline phosphate, and decrease in the level of osteocalcin in rats in diabetic group compared with other groups; these parameters improved in other groups, especially in diabetes/insulin/PTH group. The rats in diabetic group showed statistically significant decrease in neck and shaft diameters and weight of femur bone compared with other groups, while rats in diabetes/insulin/PTH group showed a significant improvement of these parameters. In diabetic group, there were different histopathological changes in cortical bone and Haversian canals, which improved in other groups, especially in rats in diabetes/insulin/PTH group. CONCLUSIONS: The untreated DM resulted in dramatic reduction in BMD and morphometric parameters. Treatment with insulin ameliorated these effects to some extent, while PTH co--treatment had a more positive effect. The combination of PTH and insulin resulted in stronger improvement of all parameters to approximately like those of control rats.