Evaluation of the beneficial efficacy of curcumin on experimental lung fibrosis of adult male albino rats: a light and electron microscopic study

Idiopathic pulmonary fibrosis is one of the major types of potentially lethal lung diseases. Curcumin, a natural phenolic compound of Curcuma longa Linn, has anti-inflammatory and antioxidant activity. It is a potent inhibitor of reactive oxygen-generating enzymes. The objective of this study was to evaluate the beneficial efficacy on curcumin on experimental lung fibrosis induced by carbon tetrachloride [CCl [4]] on adult male albino rats. A total of 32 adult male albino rats were divided into four groups. Group I [four rats] was the control group. Group II [eight rats] was further subdivided into two equal subgroups; subgroup IIA was given corn oil [1 mg/kg orally] and subgroup IIB was given curcumin [100mg/kg orally, daily]. Group III [10 rats] was given CCl[4] [1ml/kg twice a week by intraperitoneal route] and group IV [10 rats] was given curcumin 1 week before and concomitantly with CCl[4] injection. Half of the rats of each group were sacrificed after 2 weeks [subgroup A, for short-term study] and the other half were sacrificed after 5 weeks [subgroup B, for long-term study] Lung tissues were processed for light microscope [L/M] and electron microscope [E/M] studies. Moreover, morphometric study was carried out. Subgroup IIIA [short-term study] showed a nonsignificant increase in the mean area percentage of collagen fibers and a nonsignificant decrease in the number of type II pneumocytes. Lung sections revealed local areas of interstitial inflammatory reaction, intra-alveolar hemorrhage, edema, and congestion of pulmonary vessels. Subgroup IIIB [long-term study] revealed a highly significant increase in the mean area percentage of collagen fibers and a significant decrease in the number of type II pneumocytes. Lung sections showed diffuse interstitial inflammatory reaction, foci of necrotic alveolar walls, and diffuse interstitial accumulation of collagen. E/M examination revealed degenerative changes and necrosis of type I and II pneumocytes. The alveolar macrophages showed signs of activation. For 2 weeks the curcumin-supplemented group [subgroup VIA] showed an improvement in their histological findings, as revealed by the significant increase in the number of type II pneumocytes that appeared activated. Type I pneumocytes appeared healthy. After 5 weeks [subgroup VIB], there was more improvement as revealed by the highly significant decrease in the mean are percentage of collagen fibers, highly significant increase in the number of type II pneumocytes, and very minimal inflammatory reaction. Curcumin has an ameliorating effect against lung damage induced by CCI[4]. Thus, this study introduces curcumin as one of the natural herbal remedies that could act as a potential preventive agent against interstitial pulmonary fibrosis. Addition of this compound to the food of those individuals who are vulnerable to interstitial pulmonary fibrosis is recommended

Effect of rosiglitazone [PPAR-yligand] on cyclosporine induced chronic nephrotoxicity in rats: histological, immunohistochemical and biochemical study

Cyclosporine A [CsA] is the first choice immuno-suppressant used for prevention of allograft rejection. However CsA therapy is associated with nephrotoxicity. Rosiglitazone [RGZ] is used as anti-diabetic drug. It has anti-inflammatory and anti-fibrotic effect in non diabetic renal diseases. Of this work was to investigate whether the renal dysfunction and the histological changes induced by CsA in rats could be modified by concomitant administration of RGZ. Forty adult male albino rats were classified into 4 equal groups; GI served as control, received saline orally daily. G II received olive oil orally daily [vehicle for C5A]. G III was given CsA orally [15 mg/kg/day]. G IV was given RGZ orally [3mg/kg/day] and CsA as in Gill. The period of the study was 28 days. The body weight [B.W] and the systolic blood pressure [SBP] were recorded for each rat. Urine creatinine, blood urea nitrogen [BUN], serum creatinine [SC] and creatinine clearance [CCI] were calculated. Rats were sacrificed and both kidneys were removed; one was processed for detection of malondialdehyde [MDA] and the other was processed to prepare paraffin blocks. Sections were stained with HandE, Masson's Trichome and PAS stains. Other sections were processed for immuno-histochemical demonstration of caspase-3. Revealed a significant increase in SBS, BUN, SC and tissue MDA and significant decrease in BW and CCL of CsA-treated rats [G III]. Histological examination revealed tubular cell atrophy, glomeruloscierosis, focal interstitial fibrosis, inflammatory cell reaction, vascular congestion and arteriolar hyalinosis. Also, strong PAS reaction and immune expression of caspase-3 were detected. Administration of RGZ with CsA [GIV] resulted in significant improvement of renal functions and morphology compared to Cs A-treated group. That RGZ has a protective effect in nephrotoxicity induced by CsA administration. It is postulated therefore that PPAR-y ligands were important for prevention of CsA nephrotoxicity. However, their usefulness in human need to be verified

possible beneficial effect of angiotensin II receptor antagonist [Losartan] in experimental-hepatic fibrosis in albino rats. histological immunohistochemical and biochemical study

Hepatic fibrosis is a histological change caused by liver inliammation and characterized by accuix of extracellular matrix protein [ECM]. Losartan is one class of drugs that inhibit the action of angiotensin II [A' H at its receptors. It has been used as antihypertensive in human. Was to clarify the beneficial effect of losartan in experimental liver fibrosis by bile duct li-z. Forty adult male albino rats were divided into four equal groups; GI [control], Gil operated], Gill [bile duct ligated, BDL] and G VI received losartan at a dose of 5 mg/kg daily after BDL. After fc weeks, blood samples were collected for estimation of serum bilirubin [SB], alanine aminotransferase [ALT], aspare aminotransferase [AST], alkaline phosphatase [ALP] and serum hyaluronic acid [SHA]. Rats were sacrificed and th livers were processed for estimation of hydroxyproline and for histological study. Paraffin sections were stained b H and F, Masson's trichrome and other sections were stained immunohistochemically for desmin. Revealed elevated liver enzymes, serum and tissue fibrosis markers [hyaluronic acid and hydrox-cr together with dramatic histological changes in liver sections of G III [BDL]. Administration of Losartan after BDL C-V showed improvement of biochemical analysis of liver enzymes, fibrosis markers and amelioration of the his o1oria changes of hepatic tissues. Moderate expression of desmin from hepatic stellate cells [HSCs] was also evident Fr this study. That losartan has a benifical effect in liver fibrosis induced by BDL. However, further study for its usefulness in human hepatic fibrosis is recommended

Histological study on the effect of heat stress on cardiac muscle of adult male albino rats and the possible role of mast cells

Heat stress causes serious physiological dysfunction that may result in heat related diseases. The cardiovascular system has been considered the primary target of heart stress. The mechanism of heat stress- induced myocardial damage remains unclear. Recent findings indicate that mast cells are not only necessary for allergic reaction, but they also involved in a variety of neuro inflammatory diseases especially those worsened by stress. This work was aimed to study the effect of heat stress on the myocardium of rats and to clarify the possible role of mast cells in this process. This study was performed on 30 adult male albino rats, divided into three equal main groups [10 rats/ each]; the first main group was control, divided into two equal subgroups [5 rats/ each], the first subgroup [A] was negative control, the second subgroup [B] received 1 ml sterile saline I.P daily for 15 days. The second main group was heat-stressed group which was exposed to heat stress [39°C for 2 hours daily] and the third main group was mast cell stabilized group that received 10 mg/kg/b.w of doxantrazole followed by exposure to heat stress [the same as the second main group], half an hour after drug intake. All rats were sacrificed after 15 days and heart sections were processed. Paraffin sections were stained with H and E, masson trichrom [M.T] and toluidine blue for histological study. Other sections were processed for immuno histochemical demonstration of actin and caspase- 3. Other very small pieces of heart sections were processed for electron microscopic study [E.M]. The cardiac muscle of stressed second group revealed focal areas of necrosis, areas of vaculations with loss of characteristic striations and mononuclear cell infiltration. Congestion and extravasation of blood with odema fluid between cardiac muscle fibers were evident. Excessive collagen fibers deposition was also seen. Decreased reaction for actin and strong+ve reaction for caspase-3 in the affected fibers were demonstrated. Moreover hyperplasia and activation with degranulation of mast cells were documented in C.T endomesium. On ultrastructural level, the same group showed disorganized and fragmented microfilaments and mitochondrial changes. Moreover, degranulated mast cells were documented in the C.T endomesium. On the other hand, non of these changes were observed in cardiac muscles of mast cell stabilized group with the exception of slight congestion and minimal fibrosis in the interstitium and perivascular areas at light microscopic level. It is concluded that heat stress induced histological and ultra structural changes in myocardium and these changes could be mast cell mediated. Such study provided further support for the role of mast cells in stress induced myocardial damage and therefore it might provide a novel medical strategy and therapeutic target in management of heat stress induced cardiomyopathy. Furthermore, stress exposure should be avoided or minimized as much as possible to seek for good health

Histological and histochemical study of the effect of levodopa on the neuro - endocrine cells of suprarenal medulla in adult male rabbit

Parkinsonism is the disease of nigrostriatal dopamine deficiency. The symptoms of the disease are due to central dopamine depletion. L-Dopa, is the most effective therapeutic agent presently available for treatment of parkinsonism. It is extensively decarboxylated in liver to dopamine [can't cross the blood brain barrier]. Only small amount reach the brain as L-DOPA through the blood brain barrier. Most of the peripheral effects are due to its pharmacologically active metabolite dopamine. However, the mechanism of these effects is still unknown. This work was performed to study the effect of L-DOPA as antiparkinsonian drug on the neuro-endocrine cells of the suprarenal gland. The study included four equal groups of adult male rabbits [10 in each]. The animals of the first two groups were given distilled water and served as controls. The animals of the last 2 groups were received 35mg/kg body weight/day of L-DOPA orally for two and six months respectively. Paraffin sections were prepared and stained with Hx and E, Pascaul's stain, Singh modification of Masson Hamperl and chromaffin reaction for adrenaline, noradrenalin and dopamine. The results showed apparent crowdness and packing of the medullary cells exerted by the trophic action of the drug and its metabolites. There was also sinusoidal dilatation produced by direct action of the drug and its metabolite dopamine. With different stains; the neuro-endocrine cells progressively enlarged in size, apparently increased in number with increased intensity of their cytoplasmic granules. This explains their ability to uptake and decarboxylate amine precursors into amines. Their apparent increase in number and hormonal secretion may explain the causes of cardiac arrhythmia affecting the patients receiving this drug

Role of zinc administration on the effect of lead on the ovary of adult female albino rats. Histological and histochemical study

The risk of lead exposure and lead poisoning has been a major area of concern for several years mainly for women in both industrialized and developing counteries. The present study was designed to investigate the effect of chronic lead exposure on the ovary of adult female albino rats, and the role of zinc supplementation. Thirty adult female virgin albino rats were utilized in this study. They were classified into three equal groups, the 1[st] group was administered 1ml dist. Water orally and served as control group. The 2[nd] group [Lead - treated group] was administered lead acetate at a dose of 50 mg/kg b.wt. orally. The 3[rd] group [Zinc - supplemented group] was administered lead acetate as in tile 2[nd] group and zinc sulphate at a dose of 1mg /kg b. wt. orally. At the end of three months, animals were killed and ovaries were dissected out, fixd in 10% formol saline and processed for histological and histochemical studies using Hx, E, Masson Trichrome, PAS and Methyl Green and Pyronine stains. Tile histological and histochemical results revealed that chronic lead exposure resulted in degenerative changes in the ovaries and these changes were ameliorated with coadministration of zinc. This protective effect of zine could be attributed to differential distribution of lead, either because of competition between lead and zinc or displacement of lead by zinc

Study of testicular histology and histochemistry of albino rats after cyproterone acetate administration

The search for safe, effective and reversible contraceptive methods for men is an important goal to increase the available choices for couples to regulate their family size.This work was planned to study the histological and histochemical changes in rat testis after administration of cyproterone acetate [C A]; which is potent synthetic antiandrogen. The reversibility of these changes after arrest of the drug had also been studied. Thirty five adult male albino rats were utilized in this study. They were divided into control [14 rats] and treated [21 rats] groups. The control group was administered 1 ml distilled water orally daily. The treated group was subdivided into two subgroups; the 1[st] subgroup [9 rats] was administered CA at a dose of 1 mg /100 gm body, weight/day orally for one month. Three rats were sacrificed after that period and the others [6 rats] were further subdivided into 2 groups and left without treatment for one and two months. The 2[nd] subgroup [12 rats] was administered the same dose of the drug for two months. Three rats were sacrificed after that period and the others [9 rats] were further subdivided into 3 groups and left without treatment for one, two and three months. At the end of the estimated periods, testicular specimens were processed for histological and histochemical studies. Results revealed that CA produced degenerative changes in the testes in the form of disorganization, exfoliation of the spermatogenic cells and tubular shrinkage together with hyperplasia of the interstitial cells and congestion of the vasculature. An increase in PAS +ve reaction and decrease in methyl green-pyronin reaction were observed. These changes were time dependant and reversible 3 months after arrest of the treatment. It is concluded that CA could be used as reversible male contraceptive drug for short period of time. However, studying its effect on male fertility for long period of time in combination with androgen ester together with frequent assessment of serum testosterone is recommended

Potentiation of simvastatin induced-myotoxicity by cyclosporin A in rats

To study the potential effect of simvastatin, a hypocholesterolemic drug, to induce myopathy with or without cyclosporin A, 36 rats were included. Rats were treated for one week peroid and were classified into 6 groups [6 rats each]. Group I [control group]; given 0.5 ml gum tragacanth suspension orally + 0.5 ml S.c. saline daily. Group II; given 50 mg/kg /day simvastatin in gum tragacanth orally + 0.5 ml S. C.saline. Group Ill; given 100 ml/kg/ day simvastatin in gum tragacanth orally + 0.5 ml S.c. saline. Group IV; given 50 mg/kg/daysimvastatin orally+ 10 mg/kg/day S.C. cyclosporin A. Group V; given 100 mg/kg/day simvastatin orally + 10 mg/kg/ day S.c. cyclosporin A. Group VI; given 10 mg/kg/ day S.C. cyclosporin A + 0.5 ml oral gum tragacanth daily. At the end of one week, blood samples were collected and the sera were assayed for total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and creatine.phosphokinase. Skeletal muscle specimens were dissected and were fixed either in 10% formal saline or in 3% gluteraldhyde in 0.1 M phosphate buffer [pH 7.3]. Specimens were processed and stained with HX.E and Van Gieson stains for light microscopic study and with uranyl acetate and lead citrate for electron microscopic study. Results showed that simvastatin in small dose [50 mg/kg] [G II] produced minor skeletal muscle changes evidenced by presence of cloudy swelling of the muscle fibers and mononuclear celullar infiltrates. However, large dose of simvastatin [100 mg/kg] [G Ill] was associated with more severe degenerative changes, inflammatory cell reaction and necrosis of the muscle fibers with mitochondrial darnage and multiple inclusion bodies. These changes were more evident with coadministration of cyclosporin A to either small or large doses simvastatin-treated rats [G IV and V]: The serum creatine phosphokinase levels were increased in all treated groups [G II to VI] compared with control group [G I]. The enzyme level reaches a significant degree only in the high dose combination group [G V] compared with conrtol group [1306.8 +/- 87.76 Vs 566.17 +/- 59.58 IU/L, P <0.05]. Thus, simvastatin can produce skeletal muscle damage in rat in short-term peroid.The myopathic changes were dose related.and were potentiated by concomitant use of cyclosporin A. It is recommended to extend the study for a longer period