Dominance of Pro-Inflammatory Cytokines Over Anti-Inflammatory Ones in Placental Bed of Creta Cases.

Objective: The objective of the study is to investigate changes occurring in key inflammatory cytokines at molecular level (including genetic and protein) in placental bed of placenta creta compared to that of normal placenta and their correlation to interstitial extravillous trophoblasts (EVT) number. Subjects and Methods: Case-control study including placentas of patients with invasive placentation (creta placentas, n = 19) compared with those of normal placentation (n = 19). Besides routine histology and immunocytochemistry detection (cytokeratin-7 [CK-7]), addition to biochemical evaluation of expression of various cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), IL6, IL-1RA, IL-8, IL-10, and IL-13 was carried out. Results: Routine histological examination of placentas of creta cases revealed CK-7+ extravillous trophoblasts (EVT) penetrating deeply the myometrium with various histopathological arrangements and trophoblastic vascular invasion of the deep myometrial blood vessels. A significant increase (P < 0.05) in the mRNA expression of TNF-α, IL-1 ß, and IL6 with an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 was observed in creta cases compared to the control ones. A corresponding significant increase was detected in the protein levels of TNF-α, IL-1 ß, and IL-6 as well as an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 in creta cases compared to the normal ones. Moreover, we displayed a significant positive correlation (P < 0.05) between interstitial EVT number and mRNA expression of almost all pro-inflammatory cytokines with negative but insignificant correlation with anti-inflammatory cytokines in creta cases. Conclusion: The upregulated pro-inflammatory cytokines and the correlation of their expression with the increased interstitial EVT provide a supporting evidence of their potentially more relevant role in the development of placenta creta than the anti-inflammatory ones.

Pioglitazone Induces Dysplastic Urothelial Changes in Urinary Bladder of Experimental Diabetes.

Objectives: Pioglitazone (PIO) is a widely prescribed oral antidiabetic drug that has concerns regarding a potential risk of developing carcinoma of the urinary bladder. The objective of the current study was to assess this potential risk. Materials and Methods: The potential risk of PIO-induced urinary bladder carcinoma was assessed in the current study by examining urinary bladder of rats for urothelial cytokeratin (CK) expression and proliferative activity by Ki67 immunostaining. Results: Histological examination revealed dysplastic urothelial changes in PIO per se and diabetes mellitus + PIO (diabetic rats receiving PIO). In addition, a significantly (P < 0.05) decreased CK7 and CK8 expression together with a significantly increased CK20 as well as Ki67 expression was detected in the urothelial cells of groups administrated PIO, contrary to those which did not. Conclusion: The manifestations of urothelial dysplasia evidenced by histological examination as well as by the aberrant expression in CK and Ki67 after PIO administration add supporting evidence at cellular and experimental level to the previous clinical suspicions.

Thymoquinone Upregulates Catalase Gene Expression and Preserves the Structure of the Renal Cortex of Propylthiouracil-Induced Hypothyroid Rats.

BACKGROUND: The association between hypothyroidism and renal diseases has been described in many studies. Nigella Sativa was among the recently reported natural product that has the potential to prevent renal tissue damage and fibrosis. The aim of this study was to evaluate the possible protective effect of thymoquinone on the structure of the renal cortex of hypothyroid rats and explore the mechanism behind it. METHODS: An experimental model of hypothyroidism was induced in adult male Wistar rats by administration of propylthiouracil (6 mg/kg/body weight). One hypothyroid group was treated with thymoquinone at the dose of 50 mg/kg/body weight and compared to the untreated group. Thyroid function and oxidant/antioxidant status were assessed in the serum. Catalase gene expression was assessed using the real-time polymerase chain reaction. The kidney was assessed both histologically and immunohistochemically. RESULTS: Administration of propylthiouracil resulted in a significant decrease in the serum levels of nitric oxide, reduced glutathione, and superoxide dismutase activity while the level of malondialdehyde significantly (p < 0.001) increased. Administration of thymoquinone alleviated this effect on the thyroid hormones and significantly increased the serum levels of antioxidants. Thymoquinone significantly (p < 0.001) upregulated catalase transcription by about 24-fold and could block the hypothyroidism-induced glomerular and tubular injury. CONCLUSION: Thymoquinone may have a potential protective effect against hypothyroidism-induced renal injury acting through the attenuation of the oxidative stress and upregulation of renal catalase gene expression.

Quercetin mitigates monosodium glutamate-induced excitotoxicity of the spinal cord motoneurons in aged rats via p38 MAPK inhibition.

Various studies reported the possibility of deterioration of blood-brain barrier (BBB) integrity owing to the aging process. The current work was performed to investigate the ability of Monosodium glutamate (MSG) to cross BBB in aged rats, the damage affecting the anterior horn cells of the spinal cord due to excitotoxicity, and the mechanisms by which quercetin (Que) administration might suppress such damage. Forty male rats aged 18 months were assigned equally to 4 groups: control group, Que group (received Que, 20 mg/kg/d intraperitonealy for 10 days), MSG group (received MSG, 4.0 g/kg/d subcutaneously for 10 days), MSG + Que group (received both Que and MSG as done in the Que and MSG groups respectively). Cervical spinal cord specimens were obtained and prepared for routine histological study, immunohistochemical staining by caspase-3 and glial fibrillary acidic protein (GFAP), assessment of oxidative stress, measurement of cytokines, assessment of caspase-3 activity and GFAP levels as well as for western blotting of phosphorylated activating transcription factor 2 (ATF2pp) as an indicator for the activity of p38 mitogen-activated protein kinase (MAPK). The MSG group revealed variable degenerative and apoptotic changes in the motoneurons and neuroglia, a marked rise in the cytoplasmic caspase-3 expression in motoneurons and a significant reduction (p < 0.001) in the astrocyte surface area percentage. In addition, the spinal cord tissue exhibited a significant elevation (p < 0.001) in the levels of malondialdehyde (MDA), IL-1, IL-6, TNFα, INFÉ£, caspase-3 activity and ATF2 pp expression as well as a significant reduction (p < 0.001) in SOD, IL-10 and GFAP levels compared with the control group. On combining Que with MSG, most of the degenerative changes were reversed and all the impaired parameters were nearly normalized except for IL-6 and GFAP levels which were still significantly (p < 0.05) different from those of the control group. Our study suggests that MSG can break through the BBB of the aged rats and induce excitotoxicity dependent changes in spinal cord motoneurons. Most of these changes were reversed by Que probably via targeting the p38 MAPK-ATF2 pathway, antagonizing oxidative stress, anti-inflammatory effect, and promoting GFAP expression.

Impact of vildagliptin on vascular and fibrotic remodeling of myocardium in experimental diabetic cardiomyopathy.

The effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on myocardium in diabetic cardiomyopathy (DCM) remains a matter of debate. In the current study we investigated the effect of vildagliptin (VILDA, 3 mg/kg/d) on myocardium of DCM focusing on coronary microcirculation as well as on endothelial stress markers (ICAM and VCAM). We divided animals equally into 4 groups; nondiabetic (ND), VILDA per se, DCM and DCM + VILDA and their myocardium was evaluated for the fibro-vascular remodeling immunohistochemically as well as for molecular changes. VILDA had reversed the histological changes occurred in DCM including the disintegration, degeneration, and steatosis of cardiomyocytes with disappearance of the edema fluid. In addition VILDA significantly increased (p < 0.05) density of the coronary microcirculation and relieved endothelial stress. However, it did not prevent the development of fibrotic remodeling including the increased collagen deposition and the significantly upregulated (p < 0.05) corresponding genes. Therefore VILDA may have a positive impact on the microvascular remodeling, but not on fibrotic changes, in DCM.

Modulatory effect of empagliflozin on cellular parameters of endocrine pancreas in experimental pre-diabetes.

The effect of empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on the structure of endocrine pancreas in pre-diabetes (Pre-DM) is not yet elucidated. In the current study the relatively enlarged islets of Langerhans seen in the Pre-DM group was restored to control size by administration of EMPA. In addition the disbalance in the percentage of ß-cells and α-cells in islets of the Pre-DM was corrected in the Pre-DM + EMPA group with reversal of the significantly increased islet mass, ß-cell mass and neogenesis. Administrating EMPA in Pre-DM decreased level of caspase-3, increased that of Bcl-2 to control level and reduced the significantly increased inflammatory cytokines to levels approximated to those of the control group. In Pre-DM + EMPA group, EMPA had efficiently restored the significantly impaired glucose hemostasis to levels nearly similar to those of the control animals. This may indicate that the modulatory effect of EMPA on cells of the islets in Pre-DM is associated with a local pleotropic effect on inflammatory cytokines.

Increased mast cell number is associated with a decrease in beta-cell mass and regeneration in type 2 diabetic rats.

The role of mast cells (MCs) in type 2 diabetes (T2D) is not thoroughly studied as much as in T1D. Therefore in the current study we investigated correlation between these cells and various parameters of islets of Langerhans (IOL) in rats which were equally divided (n = 40) into; control and diabetic groups. We detected a significantly increased (p < 0.05) MC count (MCC) in the diabetic IOL compared to the control, together with a noticeable intra-islet seeding of these cells which displayed a tryptase positive immunostaining. A significant positive correlation (p < 0.05) between MCC and the % of glucagon cells per islet was detected in DM, unlike mass of the islets, mass of ß-cells, and % of ß-cells per islet which were negatively correlated with MCC. Similarly, there was a negative correlation between MCC with ß-cell proliferation and neogenesis frequency in DM. This highlights the potential association between the increased MC number and the diminished islet`s mass as well as regeneration which may fasten the progression of T2D.

Correlation between pancreatic mast cells and the low grade inflammation in adipose tissue of experimental prediabetes.

The role of mast cells (MCs) in prediabetes (Pre-DM) is not clearly elucidated. In the current study rats (n = 22 each) were divided equally into; control and Pre-DM (received high fat diet, HFD) groups. Samples from pancreas as well as from visceral adipose tissue (VAT) were studied for the consequent changes. We detected a significantly increased mast cell count (MCC) in the pancreas of Pre-DM compared to that of control. Frequent degranulation of MC granules was observed in Pre-DM. VAT of the Pre-DM had significantly increased (p < 0.05) macrophages (CD68+) and mast cells (tryptase+) compared to that of the control. A significant increase (p < 0.05) in CD68 mRNA expression as well as in the level of IL-1 ß, IL-6, TNF-α and TGF- ß1 was detected in VAT of Pre-DM with a significant positive correlation (p < 0.05) with the MCC. All these findings may indicate a potential role of MC in the low grade inflammation of VAT in Pre-DM.

Dysplastic urothelial changes accompany empagliflozin administration in urinary bladder of experimental diabetes.

Empagliflozin (EMPA) is a promising novel antidiabetic drug; however, doubts have been raised regarding its use and the increased risk of urinary bladder carcinoma. In this study, we evaluated urothelium expression of cytokeratins (CKs) and Ki-67 proliferative activity in the urinary bladder of diabetic (DM + EMPA) and non-diabetic rats after EMPA administration. By routine histology, dysplastic changes were detected in the urothelium of diabetic as well as non-diabetic animals after EMPA administration. Moreover, the expression of CK-7 and CK-8 was significantly decreased (P < .05) while that of CK-20 as well as Ki-67 was significantly increased (P < .05) in EMPA per se and DM + EMPA urothelium groups compared to that of control and diabetics. The dysplastic changes together with the increased proliferative activity in urothelium after EMPA administration provide a cellular evidence that supports the former clinical concerns.

Favorable outcomes of metformin on coronary microvasculature in experimental diabetic cardiomyopathy.

Although metformin is widely prescribed in diabetes, its use with associated cardiac dysfunction remains debatable. In the current study, we investigated the effect of metformin on coronary microvasculature in experimental diabetic cardiomyopathy (DCM) induced by streptozotocin. Administration of metformin after induction of DCM, reversed almost all cardiomyocyte degenerative changes induced by DCM. Metformin diminished the significantly increased (p < 0.05) collagen deposited in the DCM. In addition metformin had improved the density of the significantly decreased arteriolar (αSMA+) and capillary (CD31+) coronary microvasculature compared to that of the DCM and non-diabetics (ND) with downregulation of the significantly increased expression (p < 0.05) of COL-I, III, TGF-ß, CTGF, ICAM and VCAM genes. Therefore metformin may be beneficial in limiting the fibrotic and the vascular remodeling occurring in DCM at the genetic as well as the structural levels.

Molybdenum bupropion combined neurotoxicity in rats.

Heavy metal toxicity is a common foodborne problem in Egypt, especially in combination. Molybdenum toxicity has been studied as a model of the heavy metal toxicity. Molybdenum could promote toxicity via oxidative-inflammatory mechanisms. Bupropion is a well-known antidepressant that has anti-oxidant mechanisms. It exerts a cytoprotective action against molybdenum induced metal toxicity. The aim of the study is to evaluate the effects of combined bupropion and molybdenum in a toxic animal model. The results showed that the combination of bupropion and high doses of molybdenum was extremely toxic with an evident animal fatality. Bupropion showed a clear anti-oxidant/anti-inflammatory profile detected by the ELISA assay of malondialdehyde (MDA), reduced glutathione, and interleukin -6 (IL-6), and real-time gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and tumor necrosis factor-α (TNF-α). The immunohistochemistry of nuclear factor Kappa Beta (NF-κB) showed that bupropion reduced the inflammatory response induced by the molybdenum neurotoxicity. Despite the improved laboratory profile, the animals were extremely intoxicated with recorded fatalities raising the question about other pathways and mechanisms explaining the drug metal interaction. Furthermore, Bupropion even in normal doses was toxic to the animals. Choroid plexus hyperplasia was reported in the histological examination of the animal brain loaded with bupropion, and choroid plexus papilloma was recorded in the combined drug metal group. More wide-scale studies are needed to verify the safety of the current antidepressant medications for the long-term therapy. It is important to focus on drug metal interaction as a possible cause of neuropathology.

Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

BACKGROUND: Depression is one of the important world-wide health problems. OBJECTIVES: This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. MATERIALS AND METHODS: Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). RESULTS: OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. CONCLUSION: Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies.

Vascular and cellular changes accompany altered expression of angiopoietins in placenta of non-complicated ART pregnancies.

BACKGROUND: ART is steadily performed for infertility cases and most of the previous researches have focused on complicated pregnancies. Nonetheless, few ones have concerned with placenta of ART in non-complicated pregnancies. OBJECTIVES: To investigate the expression of angiopoietins (ANG) and their receptor, TIE-2, in placenta of full-term non-complicated pregnancies having ART (n=28) versus those with spontaneous conception (n=28) together with the histological as well as morphometric analysis. RESULTS: While no prominent changes were noticed in the histological structure of the placenta ART pregnancies, it showed a significant decrease (p<0.05) in the percentage of syncytial area and numbers of syncytial knots with insignificant reduction in the placental villous area. Vascular changes in the form of significant decrease (p<0.05) in the chorionic vessel diameter and significant increase (p<0.05) in percentage of vessel area were detected in the ART placenta. In addition, the levels ANG-1, ANG-2 and TIE-2 were significantly increased (p<0.05) in the ART placentas compared with those of SC. CONCLUSIONS: We demonstrated that there is an altered expression of angiopoietins accompanying the morphometric changes occurring in placenta of ART pregnancies. These changes may indicate vascular and cellular adaptation mechanism for a potential subclinical hypoxia in placenta of ART even in non-complicated pregnancies.

Pattern of adhesive molecules expression in placenta of non-complicated ART pregnancies.

OBJECTIVE: To investigate changes occurring in the morphometric parameters of chorionic villi and their vessels as well as in adhesive molecules expression in placenta of ART pregnancies. METHODS: Case-control study including a total of 52 placentas of non-complicated pregnancies of women delivered by spontaneous conception (SC) (n = 26) compared with those of ART (n = 26). Histological and morphometric assessment of fetal chorionic villi as well as the expression of various adhesive molecules (ICAM-1, VCAM-1 and PECAM-1) were performed in fetal plasma and placenta. RESULTS: Although we did not observe any obvious changes in the histological structure of placenta of ART pregnancies, it showed a significant (p < 0.05) decrease in the syncytiotrophoblast cytoplasmic area accompanied with a significant increase (p < 0.05) in the vessel area and syncytiotrophoblast nuclear area without remarkable change in the total villous area or total syncytiotrophoblast % area. In addition, almost all levels of the assayed adhesive molecules were significantly increased (p < 0.05) in placenta as well as in fetal plasma of ART pregnancies compared with SC. CONCLUSION: We suggested in the current study that the altered adhesive molecules expression accompanying the increased vessel area and decreased syncytial cytoplasm area may indicate a subclinical endothelial stress in placenta of non-complicated ART pregnancies.

Favorable outcomes of hydroxychloroquine in insulin resistance may be accomplished by adjustment of the endothelial dysfunction as well as the skewed balance of adipokines.

Hydroxychloroquine (HCQ) has been demonstrated to reduce the risk to develop diabetes mellitus (DM). However no previous experimental study had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in insulin resistance (IR). In addition, the mechanism by which HCQ can prevent DM is not well understood. In this study, we hypothesized that the possible favorable outcome of HCQ may be partly achieved by its molecular effect on the endothelial stress markers as well as on the imparied balance of the adipokines that usually accompanies IR. A total of 54 rats were divided equally into; control, high fat diet (HFD) and HFD+HCQ groups (received standard chow, HFD and HFD+HCQ respectively). After 12 weeks, samples from pancreas as well as visceral adipose tissue (VAT) were histologically studied for the consequent changes. In the HFD group, there were mild degenerative changes and expansion of the IOL accompanied with a significantly increased (p<0.05) ß-cell area%, mass, proliferation and neogenesis as well as a significantly decreased (p<0.05) α-cell area% compared with the other groups. On combining HCQ with HFD, reversal of these changes along with correction of the impaired adipokines levels (leptin, adiponectin, resistin, visfatin and lipocalin-2) and significant decrease (p<0.05) of the vascular endothelial stress markers (sE-selectin, sICAM and sVICAM) were manifested compared with the HFD group. Therefore, HCQ favorable effects in IR may be attributed to relieving of the endothelial stress as well as normalization of the skewed balance of adipokines.

Hydroxychloroquine hindering of diabetic isletopathy carries its signature on the inflammatory cytokines.

Hydroxychloroquine (HCQ) is supposed to have favorable effects in diabetes mellitus (DM). However no previous experimental studies had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in DM. In addition, the mechanism by which HCQ acts in DM is not well understood. In this study, we hypothesized that the possible favorable effects of HCQ in DM at the structural as well as at metabolic levels could be accomplished, in part, by its anti-inflammatory action. A total of 45 rats were divided equally into; control, DM and HCQ + DM groups (received citrate buffer, 27.5 mg/kg single ip STZ and STZ + HCQ 200 mg/kg/w respectively). After 4 weeks, samples from pancreas were histologically studied for the resulting changes. The HCQ + DM group showed preservation of IOL structure, a significant increase (p < 0.05) in the ß-cell area, %, mass, IOL proliferation and neogenesis as well as correction of the significantly increased (p < 0.05) α-cell area, %, disturbed glucose homeostasis and lipid profile compared with the DM group. The significantly elevated inflammatory cytokines in the latter were lowered in the HCQ + DM group. Therefore, HCQ showed definite favorable effects on the histological as well as the metabolic profiles in DM which may be partly attributed to its anti-inflammatory action. This notable improvement of DM by HCQ deserves further studies to distinctly approve HCQ as a promising oral hypoglycemic agent.

Effect of memantine: A NMDA receptor blocker, on ethambutol-induced retinal injury.

Ethambutol (ETM)-induced retinal injury is associated with a deterioration in visual function caused by a mechanism similar to many other retinal injuries; i.e. glutamate-induced N-methyl-d-aspartate (NMDA) receptor hyperexitability. Therefore, the current study was carried out to investigate the effect of memantine (MEM), NMDA receptor blocker, on ETM-induced retinal injury. A total of 36 rats were divided equally into: group I, control, group II (ETM administration, 100mg/kg/d, orally for 4 weeks) and group III (administration of ETM+MEM, 100 and 5mg/kg/d, respectively, orally for 4 weeks). Specimens of the retina were prepared for histological study by haematoxylin, eosin (H&E) as well as for immunohistochemical study by Bcl-2, cleaved caspase-3 and glial fibrillary acidic protein (GFAP). In the ETM group, the neural retina became significantly thinner (p<0.05) and the ganglion cell layer (GCL) was the main layer affected in the form of a significant decrease (p<0.001) in its cellularity, along with an obvious increase in Bcl-2 and GFAP expression as well as caspase-3 and oxidative stress markers level compared with other groups. On the other hand, on combining MEM with ETM, the retinal thickness, NFL appearance and GCL cellularity returned to amounts nearly similar to the control group coupled with a significant decrease (p<0.05) in the detected caspase-3, Bcl-2 levels and minimal GFAP expression. Therefore, memantine could be an effective neuroprotective agent in ETM-induced retinal injury by a mechanism that may involve correction of the pro/anti-apoptotic pathways and normalization of the oxidative and Müller cell stress responses.

Vitamin E supplementation ameliorates aflatoxin B1-induced nephrotoxicity in rats.

Fungal toxins in nutrition can cause organ dysfunction or even failure. Aflatoxin B1 (AFB1)-induced renal impairment is not sufficiently studied regarding its extent and prevention. The aim of this experiment was to study the effect of AFB1 on renal cortical tissue and whether its possible harmful effect could be prevented by the conventional economical antioxidant, vitamin E. Forty rats were divided into four groups; I-IV. Group I represented the control while the others received vitamin E (Vit E), AFB1 and AFB1+Vit E, respectively. Renal cortex specimens were taken from each group after 25 days. Then, specimens were prepared for histological study by hematoxlyin and eosin (H&E), Masson's trichrome, caspase-3 as well as for ultrastructural examination and oxidative stress parameters evaluation. Data were morphometrically and statistically analyzed. In AFB1-treated group, focal tubulo-interstitial affection in the form of tubular cytoplasmic vacuolation, mitochondrial disruption, numerous lysosomes, marked increase in collagen deposition and in caspase-3 expression were observed. Glomerular impairment in the form of fusion of podocytes enlarged foot processes and thickening of the glomerular basement membrane (GBM) with loss of its trilaminar appearance were detected. In the group treated by AFB1+Vit E, there were minimal affection of the histological structure of the renal cortex as well as significant increase in the anti-oxidative parameters which were significantly decreased in the AFB1-treated group. Therefore, Vit E could be considered in wide experimental studies to be a first choice antioxidant of high cost-effectiveness in prevention of fungal toxins pro-oxidant-induced renal impairment.

Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress.

Diabetic hazard on the myocardium is a complication of diabetes that intensifies its morbidity and increases its mortality. Therefore, alleviation of diabetic cardiomyopathy (DCM) by a reliable drug remains a matter of interest in experimental research. The aim of this study was to explore the structural alterations in the myocardium induced by atorvastatin (ATOR) in DCM, induced by streptozotocin (STZ), along with the associated changes occurring in apoptosis and oxidative stress markers. Thirty-two rats were divided into four groups; group A (control), group B (non-diabetic, received ATOR, orally, 50 mg/kg daily), group C (DCM, received STZ 70 mg/kg, single i.p. injection) and group D (DCM + ATOR). After 6 weeks, left ventricle (LV) specimens were prepared for histological and immunohistochemical study by hematoxlyin and eosin, Masson`s trichrome, anti-cleaved caspase-3 stains as well as for assays of oxidative stress markers. All data were measured morphometrically and statistically analyzed. The DCM group showed disorganization of the cardiomyocytes, interstitial edema, numerous fibroblasts, significant increases in the collagen volume fraction (p < 0.001), cleaved caspase-3 expression % area (p < 0.001) and, malondialdehyde in blood (p < 0.001), in LV (p < 0.05) compared with DCM + ATOR group. The latter has LV wall thickness, relative heart weight and antioxidant activities nearly similar to the control, independent from ATOR lipid-lowering effect. Therefore, ATOR can preserve myocardial structure in DCM nearly similar to normal. This may be achieved by suppressing apoptosis that parallels the correction of the antioxidant markers, which can be considered as non-lipid lowering benefit of statins.