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.
 

Low serum levels of vitamin D have been reported as a risk factor for breast cancer. This
narrative review provides an update on the impact of vitamin D on hormone receptors, notably
estrogen receptor subunits, and gives insights on possible therapeutic interventions to overcome
breast cancer. In addition, evidence that supports the beneficial use of vitamin D as adjuvant
treatment of breast cancer is summarized. Vitamin D deficiency is significantly widespread in
patients with triple-negative tumors. Several studies have observed a possible modulatory effect
of vitamin D or its analogues on the expression of different hormone receptors in breast cancer
and increased sensitivity to tamoxifen. Vitamin D possesses anti-inflammatory and immunomodulatory
effects in patients with breast cancer, and the mechanism of action of vitamin D in patients
with breast cancer is discussed. In conclusion, vitamin D appears to have a beneficial role in the
prevention and management of breast cancer, however, large-scale, randomized controlled trials
are needed to confirm the effects of vitamin D in breast cancer prevention or treatment.