Protective Effect of Nigella sativa and Onion Extract against 5-Fluorouracil-Induced Hepatic Toxicity.

Aim: The present study intended to compare the antioxidant, anti-lipid peroxidation, and anti-inflammatory potentials of Nigella Sativa (NS) and onion extract on 5-FU-induced liver damage in rats. Material and methods: 48 rats were divided into control, control group of the onion extract, control group of the NS extract, 5-FU-treated, concomitant NS-treated, and concomitant onion extract-treated. Liver sections were processed for histological analysis (light and electron microscopic examination). Liver enzymes (ALT, AST, and ALP), inflammatory markers (TNF-α and IL-1), antioxidant markers (SOD, GSH, and GSH/GSSG ratio), 4-HNE, NF-κB, and Nrf2 were evaluated. Results: The 5-FU-treated group exhibited inflammation, congested hepatic sinusoid, and steatosis. Improvement with few pathological residues was seen in the concomitant extract-treated groups. The 5-FU-treated group showed higher liver enzymes. The enzymes decreased in the concomitantly treated groups. 5-FU induced liver damage through oxidative stress, inflammation, and lipid peroxidation. Concomitantly using NS and onion extracts resulted in a reduction in oxidative stress, lipid peroxidation, and inflammation. Conclusion: NS and onion extracts attenuated 5-FU-induced liver damage via antioxidative, anti-lipid peroxidative, and anti-inflammatory mechanisms. NS's role was exceptional when compared with onion extract.

Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage.

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.

Age-associated functional morphology of thyroid and its impact on the expression of vimentin, cytokeratins and VEGF. The role of nigella in refinement.

INTRODUCTION: Aging causes morphological and functional changes in the thyroid gland. Free radicals play a key role in the pathology of normal aging. Vimentin and cytokeratin are cytoskeletal intermediate filaments that are often used as indirect indices of tissue injury. The aim of the study was to clarify the age-related alterations in the structure and function of the thyroid gland. The relationship between oxidative/antioxidative stress markers and cytoskeletal intermediate filaments (vimentin and cytokeratin) and oxidative/antioxidative stress markers as well as vascular endothelial growth factor (VEGF) during aging were elucidated. Finally, the role of Nigella sativa (NS) oil in ameliorating age-related alterations of the structure and function of the thyroid gland was studied. MATERIAL AND METHODS: Thirty Sprague-Dawley albino rats were divided into five groups: young adult control, young adult NS-treated, late adult control, late adult NS-treated, and senile. The age of young adult, late adult, and senile rats was nearly 7, 18 and 22 months, respectively. NS oil was added to food pellets and was administered at a daily dose of 0.1 g/kg body weight for one month. The thyroid gland was dissected and fixed immediately in 10% formalin saline. The assessment of thyroid structure was based on hematoxylin and eosin, and Masson's trichrome stainings, and histomorphometric analysis of the deparaffinized sections. Localization and distribution of vimentin and cytokeratin filaments was assessed by immunohistochemistry. Measurements of VEGF gene expression by qPCR and oxidative/antioxidative markers (malondialdehyde and glutathione content, superoxide dismutase activity) in thyroid gland homogenates were performed. Serum concentration of thyroid hormones (T3, T4) and TSH were assessed by radioimmunoassay. RESULTS: Follicles in the late adult control group were dilated and disrupted. Follicular cells showed cytoplasmic vacuolation. Follicles in the thyroids of senile rats were of irregular shape, often with cellular exfoliations. Many follicles were dilated and lined with flattened cells. A notable amelioration of these morphological alterations was observed in late adult NS-treated rats. Decrease in serum T3 and T4 levels and increase in TSH levels were observed in the late adult control and senile groups. A clear shift of the oxidative/antioxidative markers (MDA/ /GSH, SOD) was observed in the late adult control and senile groups in favor of oxidants. Administration of NS to late adult rats resulted in normalization of these parameters. Increased area of collagen fibers, immunoreactivity of vimentin and cytokeratin filaments and VEGF gene expression were observed in the thyroids of late adult and senile rat groups as compared to young animals. The mean number of follicular cells decreased in the late adult control and senile groups. Administration of NS to the late adult rats returned these parameters to the level of the young adult rats. CONCLUSIONS: Aging-related alterations in both structure and function of the rat thyroid gland that are associated with increased indices of oxidative stress might be abrogated by administration of antioxidative agents present in Nigella sativa oil.

Protective Role of N-Acetylcysteine on Isoprenaline-Induced Myocardial Injury: Histological, Immunohistochemical and Morphometric Study.

Several researchers studied the protective effect of the N-acetylcysteine (NAC) when it was given before the induction of myocardial infarction (MI). Other researchers studied such protective effect when it was before done and after done of the MI. The missing data are the comparison between the protective effect of NAC before myocardial injury with its protective effect both before and after myocardial injury. The aim of the study was to compare the cardioprotective effect of NAC on the isoprenaline-induced myocardial injury before the isoprenaline (ISP) injection with its protective effect both before and after the ISP injection. This study was applied over both short and long time periods. A total of 90 male adult Wistar albino rats were used in the study. The rats were divided into four groups: control group, ISP-treated group, NAC-pretreated group and NAC-pre-& posttreated group. Based on the duration of the experiment, the second and third groups were further subdivided into a and b groups. Histological, immunohistochemical and histomorphometric analysis were used. The myocytes in the ISP-treated groups were fragmented, disrupted with karyolysis. The blood vessels were dilated, congested and associated with blood extravasation, interstitial edema and cellular inflammatory infiltration. Much improvement was observed in the NAC-pretreated group. Focal degeneration was detected in the muscle fibers. The capillaries were normal. Minimal blood extravasation and cellular infiltration were seen. The cardiac muscle fibers in the NAC-pre-& posttreated group were regularly arranged. The mean collagen fiber area percent of the ISP-treated groups was significantly higher by 8.3-folds and 10.1-folds as compared with that of the control group and was also higher by 5.5-folds and 6.8-folds as compared with that of the NAC-pre-&posttreated groups. The α-SMA area percent in the ISP-treated groups was significantly higher by 12.2-folds and 23.9-folds as compared with that of the control group and was higher by 7.5-folds and 15-folds as compared with that of the NAC-pre-& posttreated groups. The mean PCNA area percent of the ISP-treated groups was significantly higher by 126.2 and 164.8% as compared with that of the control group and was higher by 106.3 and 141.5% as compared with that of NAC-pre-& posttreated groups. ISP had deleterious effects on the heart. Administration of NAC before ISP injection could largely reduce the ISP-induced short- and long-term alterations. The protection was maximum with the use of NAC before the ISP injection and continued after the injection for 12 days.

NT-proBNP in Children With Left to Right Shunt and Dilated Cardiomyopathy.

BACKGROUND: B-type natriuretic peptide (BNP) levels are elevated in children with congenital heart disease involving a left-to-right shunt (LRS) and are also raised in dilated cardiomyopathy (DCM). As far as we know, there are few reports in the literature comparing the change of the NT-proBNP in LRS and DCM especially in the pediatric age group. OBJECTIVES: The aim of the study was to compare the changes of the NT-proBNP in pediatric patients with LRS and DCM. Correlation between the levels of NT-proBNP and the echocardiographic parameters in both groups was determined. PATIENTS AND METHODS: A total of 30 children (13 males and 17 females) participated in the study. There were 11/30 (36.7%) DCM and 19/30 (63.3%) LRS. The control group consisted of 44 healthy infants and children. Manifestations of heart failure (decompensation) were recorded. The NT-pro BNP levels were measured. The following Echo parameters were assessed: systolic function (ejection fraction and fraction shortening), pulmonary to systemic flow (Qp/Qs) in LRS, pulmonary flow and pulmonary artery pressure (SPAP) and LV diastolic function (E-wave, A-wave, E/A ratio and deceleration time). RESULTS: Clinically 17/30 (56.7%) (11 of the LRS and 5 of the DCM) were decompensated. Significant shunt was present in 15/19 (78.9%) in LRS. Systolic dysfunction was presented in 5/30 (16.7%) cases (4 patients were DCM and one case was LRS). Two types of diastolic dysfunction, impaired relaxation in 5/22 (22.7%) patients and restrictive-like filling pattern in 5/16 (31.2 %) were observed. The NT-Pro BNP level was significantly elevated 11 and 16 times in the LRS and DCM groups respectively. Negative significant correlations were observed between the levels of NT-ProBNP and the following echo variables; EDD, LAD, E wave and E/A ratio in the LRS patients. Positive significant correlations were observed between the levels of NT-ProBNP and the following echo variables; PAP and QP/QS in the LRS. Both the PAP and QP/QS were higher in the elevated NT-Pro BNP group compared to the normal level group. The NT-Pro BNP level was elevated in all 17/30 (56.7%) decompensated patients (11 were LRS, 6 were DCM) (P = 0.002). However, the level was elevated in only 7/13 (23.3%) of the compensated patients (3 were LRS, 4 were DCM) (P = 0.002). The NT-Pro BNP level was also elevated in 18/19 cases with pulmonary hypertension (P = 0.01). Finally, we conclude that the NT-ProBNP level is elevated in both LRS and DCM in pediatric age. This elevation is more remarkable with heart failure and increased PAP in both diseased groups. The level was also elevated and correlated to Qp/Qs in the LRS patients. CONCLUSIONS: So, we recommend the use of NT-ProBNP as a routine marker for following up patients with heart failure and pulmonary hypertension in LRS and DCM.

Concomitant protective and therapeutic role of verapamil in chronic mercury induced nephrotoxicity in the adult rat: histological, morphometric and ultrastructural study.

INTRODUCTION: Mercury intoxication is a widespread problem as mercury is used in the manufacture of thermometers, batteries and electrical switches. It forms one of the most diffusible environmental pollutants. Mercury has a nephrotoxic effect which could occur at low exposure levels. Verapamil could help in the treatment of mercuric toxicity. The aim of the study was to examine the protective and therapeutic effect of concomitant verapamil on chronic mercuric chloride nephrotoxicity. This was done through histological, morphometric and transmission electron microscopic studies. MATERIAL AND METHODS: Sixty adult male albino rats were used. The rats were divided into a control group and 4 experimental groups: group I (HgCl2), group II (concomitant HgCl2 and verapamil), group III (HgCl2 withdrawal) and group IV (HgCl2 withdrawal then verapamil treatment). RESULTS: Chronic administration of HgCl2 resulted in cortical nephrotoxic effects in the form of glomerular sclerosis, acute tubular necrosis and interstitial inflammatory cellular infiltration which eventually ended in interstitial fibrosis. Concomitant use of verapamil with HgCl2 improved the previous pathological changes partially. The findings in group III were less severe compared to group IV. The persistence of the pathological findings in these groups reflects the irreversible nephrotoxic changes caused by chronic HgCl2 exposure. CONCLUSIONS: We concluded that the concomitant administration of verapamil has a much better effect in minimizing the nephrotoxic effect caused by chronic HgCl2 than its therapeutic administration. So, we recommended the prophylactic use of verapamil in suspected cases of chronic mercuric chloride nephrotoxicity to preserve renal function.

Lung damage after long-term exposure of adult rats to sodium fluoride.

INTRODUCTION: Fluorides, when taken in amounts exceeding the standard therapeutic dosage, are regarded as toxic substances. Chronic fluorosis causes marked destruction of lung tissues. The study aimed to determine whether the effect of a chronic toxic dose of sodium fluoride on the lung of an adult male albino rat is reversible or irreversible. This was done through light and electron microscopic studies. Morphometric study was also done. MATERIAL AND METHODS: Forty adult male rats were used. The animals were divided into 3 groups: control group; group I (chronic fluorosis group) in which sodium fluoride was given daily for 3 months; and group II (recovery group) in which sodium fluoride was given daily for 3 months and after that the rats survived for another month. RESULTS: The lung of group I was characterized by presence of blood and lymph congestion. Thickening of alveolar septa was also observed with rupture of septa and widening of the air spaces. The area % of collagen (1.13 ±0.5), septal wall thickness (13.47 ±6.1), and number of macrophages (5 ±2.5) increased in comparison to the control group (p ≤ 0.05). With discontinuation of sodium fluoride (group II), no much improvement was observed. CONCLUSIONS: Chronic fluorosis has many pathological effects on the lung which are irreversible.

Effect of glucocorticoids on indomethacin-induced gastric ulcer in the adult male albino rat - histological, morphometric and electron microscopy study.

INTRODUCTION: Indomethacin is a non steroidal anti-inflammatory drug (NSAID) which is capable of producing injury to gastric mucosa. To prevent of NSAID-induced gastropathy, it is important to evaluate the risk factors. One of them is steroid. The aim is to study time dependent effects of glucocorticoids (GC) on indomethacin induced gastric ulcer. MATERIAL AND METHODS: Forty-nine albino rats were used. They were divided into control and experimental groups. The experimental group was subgroup I (rats were given indomethacin and were sacrificed 1 day after drug intake), subgroup II (rats were given indomethacin + dexamethasone and were sacrificed 1 day after drug intake), subgroup III (rats were given indomethacin + dexamethasone and were sacrificed 3 days after drug intake) and subgroup IV (rats were given indomethacin + dexamethasone and were sacrificed 7 days day after drug intake). Histological, scanning electron microscopy and morphometric studies were used. RESULTS: Indomethacin induced gastric ulceration with shredding of the superficial epithelial cells. The fundic glands were dilated in the subgroups II, III, IV. The surface epithelial cells were shredded and the ulcer sizes were big in subgroup IV. All subgroups exhibited abnormal surface epithelial cells within the gastric ulcer area. CONCLUSIONS: Indomethacin is capable of producing injury to gastrointestinal mucosa. With prolonged use of GC the surface epithelial cells became more affected and the ulcer sizes became bigger. Concomitant use of both medications will delay the healing of the indomethacin induced gastric ulcer and induce more gastric complication.