Objective(s):

This study was designed to investigate the effect of berberine (BBR) on diclofenac sodium-induced testicular impairment in mice.

Materials and Methods:

Eighteen male mice were divided randomly and equally into three groups for three weeks. One group was kept as control, the second group was injected intraperitoneally with diclofenac sodium (DS) at a dose of 10 mg/kg BW daily during the second and third weeks. The third group received daily oral administration of BBR at a dose of 50 mg/kg BW throughout the whole period of the experiment in parallel with the injection of the above-mentioned dose of DS during the second and third weeks. Plasma testosterone as well as testicular lipid peroxides (LPO), nitric oxide (NO), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were evaluated. In paraffin-embedded testicular tissues, histological examination, immuno-expression of glutathione reductase (GR), and TUNEL assay were carried out.

Results:

Testosterone levels were within the normal range in all groups. BBR decreased testicular LPO and induced SOD and GSH without marked changes in CAT and NO. The histology of testis was improved and, regularity and integrity of seminiferous tubules basement membranes, and distribution and amount of peritubular collagen fibers were normalized. BBR treated group showed few positive GR immuno-expression in spermatogenic cells and negative GR immuno-expression in interstitial cells of Leydig along with a few apoptotic spermatogenic cells.

Conclusion:

BBR is effective in protecting against DS-induced testicular dysfunction by improving oxidant/anti-oxidant balance and blocking the apoptotic cascade.

Introduction: Type 2 diabetes (T2D) is a widely distributed disease that affects large population worldwide. This study aimed to verify the role of Ginkgo biloba (GB) extract and magnetized water (MW) on the survival rate and functional capabilities of pancreatic βcells in type 2 diabetic rats. Materials and methods: T2D was induced by feeding the rats on a high-fat diet (20% fat, 45% carbohydrate, 22% protein) for eight weeks followed by intra-peritoneal injection of a single low dose of streptozotocin (25mg/Kg). Forty rats were randomly assigned to four groups (n=10 rats) as follows: non treated control and three diabetic groups. One diabetic group served as a positive control (diabetic), while the other two groups were orally administered with water extract of GB leaves (0.11 g/kg/day) and MW (600 gauss) for four weeks, respectively. Results: The β-cell mass and insulin expression in these cells increased markedly after both treatments, particularly in GB treated group. In addition, the immune-expression of the two antioxidant enzymes; glutathione and superoxide dismutase 2 (SOD2) in the pancreatic tissue demonstrated a down-regulation in GB and MW treated groups as compared with the diabetic group. Conclusion: A four-week treatment of GB and MW protected pancreatic β-cell cells and improved their insulin expression and antioxidant status in type 2 diabetic rats

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) with subsequent motor manifestations. This study aimed to assess the ameliorative effects of nicotine, in rotenone-induced PD rat model. Thirty adult male Albino Wistar rats were divided into three equal groups. Group I received an injection of normal saline. Group II received subcutaneous injection of rotenone at a dose of 1.5 mg/kg every other day. Group III received rotenone in the same previous dose and nicotine at a dose of 1.5 mg/kg daily. After 11 days of treatment, body weight (BW) and rat motor behavior were estimated. Specimens from the midbrain were processed for light and electron microscopy. The expression of tyrosine hydroxylase (TH), α-synuclein, and GFAP was examined. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), and striatal levels of dopamine (DA) were analyzed. Group III revealed a significant improvement in BW and motor activity. Nicotine upregulated the expression of TH, downregulated the expression of α-synuclein and GFAP. The levels of MDA and TAC were improved but were still far from those of the control. Striatal DA levels increased. Nicotine activated the neurons and glial cells. The vascular endothelium, however, did not elicit improvement. Although nicotine ameliorated the loss of the dopaminergic neurons and motor deficit, it did not show improvement of vascular endothelium. It is still necessary to examine nicotin’s ability to maintain the dopaminergic neurons in a good functioning state.

Background Hypothyroidism is a common endocrine disorder characterized by a deficiency of thyroid hormones less than the normal levels. Recent research studies identified the presence of stem cells that act as a source of tissue regeneration within the thyroid gland. Aim To investigate the role of resident thyroid stem cells on the hypophyseal thyroid axis in experimentally induced hypothyroidism in male rats. Materials and methods A total of 30 healthy male rats were randomly divided into three groups. Group I was the control group). Group II was the hypothyroid group. It received carbimazole in a dose of 0.6 mg/kg dissolved in water to induce hypothyroidism. It was administered via an orogastric tube daily for 3 months. Group III was the withdrawal group. It included hypothyroid animals, as in group II, that were left without treatment for another month and then killed to assess hypothyroidism’s recovery. The thyroid and pituitary glands were extracted from all groups and processed for histological and immunohistochemical analysis. Results The present study revealed that hypothyroidism caused marked histological changes in the pituitary–thyroid axis. Shrunken thyroid follicles with a significant increase in the epithelial height were seen. The colloid decreased in follicles or was completely absent in others. The follicular cells showed vacuolated cytoplasm. A  significant increase in the number of parafollicular cells was observed. Thyrotrophs also appeared vacuolated with an increase in their number. Increase in the apoptotic cells and vascular endothelial growth factor-immunostained cells were observed. The withdrawal group showed moderate improvement in the architecture of the thyroid and pituitary glands. These results were confirmed by the morphometric and thyroid function test analysis. Conclusion The presence of resident thyroid stem cells led to moderate thyroid structure improvement but was not sufficient to restore the normal thyroid function.

Background: Gibberellic acid (GA3) is frequently applied in agriculture to stimulate flowering & fruit growth. Owing to its persistence in the soil for months, it may cause harm to human health. Silymarin is a herbal drug commonly known as hepatoprotective agent. Aim: To reveal the outcomes of exposure to GA3 on the pancreatic functions in late days of gestation and early lactation and to elucidate the possible protective role of silymarin on these alterations if present and the pathophysiological pathways. Materials and Methods: 18 lactating Albino rats & 18 pups were classified into control group, GA3-treated group: received GA3 dissolved in drinking water (55 mg/kg/day), and silymarin & GA3-treated group: administered both GA3 & 100 mg/kg silymarin during the last week of pregnancy & the first 2 weeks of lactation. Serum levels of glucose, insulin & amylase were measured. Pancreatic tissue homogenate was used for the assessment of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), interleukin-1β (IL-1β) & tumor necrosis factor-alpha (TNF-α). Additionally, pancreatic specimens were processed for histological examination. Results: Administration of GA3 impaired pancreatic functions in dams and pups namely, elevated serum levels of glucose and amylase & reduced insulin levels accompanied with significant increased oxidative stress & inflammatory markers in pancreatic homogenate and altered the general histological pancreatic appearance. Co-treatment with silymarin potently improved these biochemical & histological alterations. Conclusion: Silymarin attenuates GA3-induced alterations in pancreatic functions through cytoprotecting actions on pancreatic exo- and endo-crine cells.

Aims: Cigarette smoking (CS) is the main cause of chronic obstructive pulmonary disease (COPD). Endothelial dysfunction is related to the severity of pulmonary disease in COPD. This study aimed to evaluate the effectiveness of single and combined administration of pioglitazone (Pio) and irbesartan (Irb) against COPD-induced endothelial dysfunction in mice and the involvement of NO and H2S in their effects. Materials and methods: Adult male Swiss mice (n = 40, weighing 25–30 g) were assigned into 5 groups. The normal control group received 1% carboxy methyl cellulose (CMC). The CS group was exposed to CS and administered 1% CMC for 3 months. The CS + Pio, CS + Irb, and CS + Pio/Irb groups were subjected to CS and received Pio (60 mg/kg), Irb (50 mg/kg), and their combination respectively, daily orally for 3 months. Body weight gain, mean blood pressure, urinary albumin, serum NO and ET-1 levels with TNF-α and IL-2 levels in lung tissue and bronchoalveolar lavage were measured. Lung H2S and ET-1 levels, protein expression of PPARγ in lung and VEGF in lung and aortic tissues with histological changes were assessed. Key findings: Our results illustrated that CS induced a model of COPD with endothelial dysfunction in mice. Pio/ Irb singly and in combination elicited protective effects against the pathophysiology of the disease with more improvement in the combined group. There is a strong correlation between NO and H2S as well as the other measured parameters. Significance: Collectively, both drugs performed these effects via their anti-inflammatory potential and increasing H2S and NO levels.

This study aimed to evaluate the histopathological and ultrastructural changes in sciatic nerve barriers after exposure to different doses of nicotine. Twenty-seven adult male rats were divided into 2 groups; group I served as control (n = 9) and group II that received nicotine (n = 18) was subdivided into two equal subgroups; group IIa and group IIb that were injected subcutaneously daily for one month with nicotine at a dose of 3 mg/kg and 6 mg/kg body weight, respectively. Specimens of sciatic nerve were processed for light and electron microscopy. Immunohistochemical expression of ZO-1 and vascular endothelium growth factor (VEGF) were investigated. Abundance of mRNA for VEGF was determined via qRT-PCR. Total antioxidant capacity (TAC), malondialdehyde (MDA), alanine transaminase (ALT) and aspartate transaminase (AST) were measured. Group IIb showed increased perineural fibrosis and myelin abnormalities. ZO-1 expression was significantly decreased. Schwann cells showed features of apoptosis and blood capillaries showed disrupted lining. High statistical difference in the level of mRNA expression of VEGF between group IIb and group I was found. There was decreased level of TAC and increased MDA, ALT and AST. A dose-dependent nicotine-induced oxidative stress on the sciatic nerve occurred via disruption of nerve barriers, altered VEGF and ZO-1 levels.

We aimed in our current study to explore the protective effect of Ginkgo biloba (GB) and magnetized water (MW) against nephrotoxicity associating induced type 2 diabetes mellitus in rat. Here, we induced diabetes by feeding our lab rats on a high fat-containing diet (4 weeks) and after that injecting them with streptozotocin (STZ). We randomly divided forty rats into four different groups: nontreated control (Ctrl), nontreated diabetic (Diabetic), Diabetic+GB (4-week treatment), and Diabetic+MW (4-week treatment). After the experiment was finished, serum and kidney tissue samples were gathered. Blood levels of glucose, triglycerides, cholesterol, creatinine, and urea were markedly elevated in the diabetic group than in the control group. In all animals treated with GB and MW, the levels of urea, creatinine, and glucose were significantly reduced (all ). GB and MW attenuated glomerular and tubular injury as well as the histological score. Furthermore, they normalized the contents of glutathione reductase and SOD2. In summary, our data showed that GB and MW treatment protected type 2 diabetic rat kidneys from nephrotoxic damages by reducing the hyperlipidemia, uremia, oxidative stress, and renal dysfunction.

Background: Recent investigations suggested that anticancer agents may inhibit the progression of Alzheimer’s
disease (AD) pathology. Conyza dioscoridis (L.) was demonstrated to have anticancer, antioxidant, anti-inflammatory and antidiabetic effects. This study was carried out to investigate the efficacy of polyphenols from Conyza dioscoridis (L.) extract (PCDE) on AD.
Methods: Impacts of 3 doses of PCDE and donepezil, a reference drug, on the features of Alzheimer’s disease in two animal models were investigated.
Results: PCDE ameliorated the memory and learning impairment shown in rats following a single dose of scopolamine (scopolamine model) or 17 weeks of high-fat/high-fructose(HF/Hfr) diet coupled with a single dose of streptozotocin, (25 mg/kg) (T2D model). They reduced significantly the high hippocampal cholinesterase activity in the two models of rats. Administration of PCDE for 8 weeks in the T2D model showed a significant reduction in hippocampal GSK-3β, caspase-3 activity and increase in the inhibited glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). A significant reduction of HOMA-insulin resistance and serum hypercholesterolemia was observed. The Tau hyperphosphorylation and Aβ 1–42 generation in the hippocampal of T2D rats were significantly decreased by PCDE. Modulation of the oxidative stress markers, (rise in GH and SOD; decrease in MDA levels) and a significant reduction of TNF-α and IL-1β in the hippocampus of T2D rats treated by PCDE extract were important findings in this study. The highest dose tested was 4% of the highest safe dose.
Conclusion: Our study suggests that PCDE is multi-targeting agent with multiple beneficial activities in combating
features of AD. This study may provide a novel therapeutic strategy for AD treatment that warrants clinical studies.