Hala M. Soliman

Interleukin-10 to tumor necrosis factor-alpha ratio is a predictive biomarker in nonalcoholic fatty liver disease: interleukin-10 to tumor necrosis factor-alpha ratio in steatohepatitis.

Objectives Fatty liver disease is commonly associated with diabetes mellitus (DM). Insulin resistance (IR) as an investigative biomarker is only concerned with fatty liver that results from DM type 2 associated with metabolic syndrome. Irrespective of IR, DM is generally characterized by overproduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-&agr;), whereas action of the latter is modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). The aim of this study was to investigate the efficacy of using TNF-&agr; alone or IL-10/TNF-&agr; ratio compared to IR, as a promising biomarker for fatty liver assessment in DM. Furthermore, we hypothesized that using garlic as an immunomodulator may decrease TNF-&agr; and increase IL-10 production to improve steatohepatitis. Methods DM was induced metabolically by a high-fat diet to bring about IR, or chemically by alloxan, producing insulin deficiency, in male albino rats. Garlic powder was supplemented (15 mg/kg per day) for 3 weeks. Fatty liver was depicted histologically and biochemically (aspartic aminotransferase, alanine aminotransferase, HOMA-IR, TNF-&agr;, IL-10, IL-10/TNF-&agr; ratio). Results We found that, in contrast to obese rats, garlic decreased IL-10/TNF-&agr; ratio, despite decreasing TNF-&agr; in alloxan diabetic rats in agreement with the histology, which revealed more prominent improvement in the obese group. Moreover, the effect of garlic was not linked to improvement of IR in obese rats. Conclusion We conclude that IL-10/TNF-&agr; ratio may be considered as a convenient biomarker for investigation of fatty liver of different grades, apart from being associated with IR, and immunomodulation of this ratio in favor of increasing it may exert significant improvement.

Turmeric-based diet can delay apoptosis without modulating NF-κB in unilateral ureteral obstruction in rats

The unilateral ureteral obstruction (UUO) model of renal injury in rat is characterized by nuclear factor κB (NF‐κB) activation and tumour necrosis factor α (TNF‐α) production, which induces apoptosis via activation of caspase 8 resulting in cell death. Curcumin, the major component found in turmeric spice, has been reported to provide protection against fibrosis and apoptosis elicited by UUO. This study examined the effects of a turmeric‐based diet (5% w/w) on the apoptotic pathway induced by UUO in rats after 30 days of ligation. Administration of a turmeric‐based diet demonstrated a significant decrease (P < 0.05) in mRNA expression of TNF‐α and caspase 8, but not NF‐κB, expression, which may contribute to the protective role of the turmeric‐based diet. We conclude that a turmeric‐based diet can delay apoptosis without modulating NF‐κB, so as not to sensitize the mesangial cells to the apoptotic stimuli.

Role of hepatic stellate cells in fibrogenesis in a model of pomegranate-treated fatty liver induced by junk food in male albino rats immunohistochemical and electron microscopic study

Introduction Hepatic fibrogenesis is a common result of liver injury. It is believed to be a critical factor that leads to hepatic failure. A critical event in fibrogenesis is activation of hepatic stellate cells (HSCs). Aim of work The aim of this investigation was to study the role of HSCs in fibrogenesis in a model of pomegranate juice (PJ)-treated fatty liver induced by junk food using immunohistochemical and electron microscopic study. Materials and methods Thirty young male albino rats were divided into control (I) and experimental (II) groups. Group II was further divided into two subgroups: II-a (junk food) and II-b (pomegranate juice + junk food). After 8 weeks, blood samples were collected for detection of leptin and tumour necrosis factor alpha TNF-&agr;.Then half of the liver samples were processed for light microscopic examination, whereas the other half were prepared for electron microscopic examination. Paraffin sections were stained using H&E, glial ibrillary acid protein, &agr;-smooth muscle actin, TNF-&agr;, and transforming growth factor -beta-1 TGF-&bgr;1. Morphometric and statistical studies for assessing immunoexpression were carried out. Results HSCs markers glial fibrilar acid protein and &agr;-smooth muscle actin and cytokines TNF-&agr; and TGF-&bgr;1 in subgroup II-a showed strong positive immunoexpression. Electron microscopic study showed activated - HSCs containing granules and collagen fibrils. Proliferative and myofibroblast -HSCs were also seen in the same group. Subgroup II-b showed a nonsignificant increase in immunoexpression of HSCs markers and cytokines. However, only activated- HSCs were seen. Conclusion and recommendation Immunoexpression of HSC markers and cytokines may be used as an indicator for liver fibrosis. Presence of different types of HSCs in fatty liver explains their role in fibrosis. Further experimental and clinical studies directed toward inhibiting the activity of HSC may delay or prevent liver fibrosis occurs in many pathological conditions.

Effect of experimentally induced portal hypertension on the fundic mucosa of adult male albino rats and the possible protective role of quercetin supplementation: histological, immunohistochemical, and biochemical study

Introduction Portal hypertension (PHT) is a hyperdynamic circulation disorder. Its precise effect on the fundic mucosa remains a matter of controversy. Aim of study Evaluation of the effect of long –term experimental induction of PHT on the rat fundic mucosa and the possible protective role of quercetin. Materials and methods Forty rats were divided into the following three main groups; control, partial portal vein ligation (PPVL) and PPVL receiving 50 mg/kg/day of quercetin given intraperitoneal. After ten weeks from PPVL induction, samples from fundus of stomach were prepared for light and electron microscope. Tissue and blood samples were examined for inflammatory, oxidative stress and antioxidant markers. The number of parietal cells, area % of collagen fibers, PAS –alcian blue reaction, nitrotyrosine- and caspase-3 positive reaction were measured morphometrically and statistically analyzed. Results Fundic mucosa of PPVL group showed loss of normal architecture, exfoliation of the surface epithelium, inflammatory cellular infiltration and congestion of blood vessels in lamina propria. Parietal cells showed dilatation of their intracellular canaliculi. Many mucous cells had apoptotic nuclei. Chief cells had few secretory granules and dilated RER. Statistically, there was significant increase in the area% of collagen fibers, nitrotyrosine, caspase- 3 and inflammatory markers while area% of PAS–alcian blue reaction, number of parietal cells and tissue antioxidant enzymes showed significant reduction comparing with the control. Quercetin markedly protect fundic mucosa from histological and biochemical deleterious effects of PHT. Conclusion PHT exerts a deleterious histological and biochemical effects on the fundic mucosa. Both antioxidant and antiinflammatory effects of Quercetin offer degree of protection for fundic mucosa, therefore, it may protect from gastropathy resulted from PHT.

Effect of Nigella sativa oil versus amoxicillin in induced chronic fundic gastritis in adult female albino rats: a histological, immunohistochemical, and biochemical study

Introduction Chronic gastritis may be due to many pathological factors, one of which is Helicobacter pylori (H. pylori) infection. Aim of work This work aimed to study the effect of Nigella sativa oil (NSO) as against amoxicillin (AMOX) on the histological changes in chronic fundic gastritis induced by H. pylori. Materials and methods Thirty adult female albino rats were divided into control (I) and experimental (II) groups. The latter group received 0.5 ml of H. pylori brucella broth in daily morning doses for 1 week. The rats were then randomly classified into gastritis (IIa), AMOX (IIb), and NSO (IIc) subgroups. Serum levels of gastrin hormone and pepsinogen I were measured. Samples from fundus of the stomach were stained with H&E, inducible nitric oxide synthetase, and DNA fragmentation factor 45. Morphometric and statistical studies were carried out. Results There was a highly significant increase in gastrin hormone level accompanied by a highly significant reduction in pepsinogen I level in H. pylori-induced gastritis. Fundus from the H. pylori subgroup showed disorganized fundic glands, wide empty gastric pits, few cytoplasm, and dark thin nuclei of surface mucous cells. Most of the parietal cells had vacuolated cytoplasm and pyknotic peripheral nuclei. Infiltrations of lamina propria by mononuclear cells and extravasated RBCs were noticed. Both moderate and strong positive immunoreactions for inducible nitric oxide synthetase and DNA fragmentation factor 45 were observed. There was a highly statistically significant increase in the number of inflammatory cells, congested blood vessels, and extravasated RBCs, and in immunohistochemically measured morphometric parameters. The subgroup of chronic gastritis rats treated by NSO showed a nearly normal histological appearance for surface mucous, mucous neck, and parietal cells. Conclusion and recommendation NSO exhibits useful histological and biochemical anti-H. pylori activity, which is comparable to that of AMOX. In the future, further experimental and clinical trials may be needed to improve the efficiency of the natural line of therapy, in addition to chemical methods of treatment.

Effect of Helicobacter pylori on the mucosa of the lower end of the esophagus in induced chronic gastritis in adult albino rats: a histological and immunohistochemical study

Introduction Although Helicobacter pylori is linked to the occurrence of chronic gastritis, its effect on the lower end of the esophagus is still an open question. Aim of work This study aimed to investigate the histological changes in the mucosa in the lower end of the esophagus after experimental induction of chronic gastritis by H. pylori, with special emphasis on changes occurring under its different lines of eradication. Materials and methods Thirty-six adult female albino rats were divided into control (group I) and experimental (group II) groups. The latter group received 0.5 ml of H. pylori brucella broth through an orogastric tube in daily morning doses for 1 week. Eight weeks later, rats of group II were further subdivided into four subgroups: IIa, IIb, IIc, and IId. Rats of the latter three subgroups were treated for an additional 4 weeks with amoxicillin, curcuminoid extract, and a mixture of both, respectively, whereas subgroup IIa underwent no treatment for H. pylori. Twelve weeks after induction of H. pylori, samples from the lower end of the esophagus were stained with H&E, Mallory’s trichrome, and nitrotyrosine immunoperoxidase and studied morphometrically. Results Subgroup IIa showed an increase in the height of the epithelium that had inflammatory infiltrations, mitotic cells, spaces separating prickle cells, and many keratohyalin granules. The lamina propria showed elongated connective tissue papillae, wide spaces, and inflammatory cells. There was a highly significant increase in the mean number of inflammatory cells, epithelial and connective tissue papillae height, thickness of keratohyalin granules-containing layer, and area% of nitrotyrosine immunostaining. Subgroup IIb treated with amoxicillin showed worsening of histological and immunohistochemical changes as well as of all morphometrically measured values. However, subgroups IIc and IId showed improvement in most of these changes. Conclusion and recommendation H. pylori treated with amoxicillin worsened the inflammatory changes, whereas curcuminoid extract improved the condition. Further studies to evaluate the use of curcumin with other anti H. pylori drugs are needed.