The myloglossus in a human cadaver study: common or uncommon anatomical structure?

BACKGROUND: Additional extrinsic muscles of the tongue are reported in literature and one of them is the myloglossus muscle (MGM). Since MGM is nowadays considered as anatomical variant, the aim of this study is to clarify some open questions by evaluating and describing the myloglossal anatomy (including both MGM and its ligamentous counterpart) during human cadaver dissections. MATERIALS AND METHODS: Twenty-one regions (including masticator space, sublingual space and adjacent areas) were dissected and the presence and appearance of myloglossus were considered, together with its proximal and distal insertions, vascularisation and innervation. RESULTS: The myloglossus was present in 61.9% of cases with muscular, ligamentous or mixed appearance and either bony or muscular insertion. Facial artery provided myloglossal vascularisation in the 84.62% and lingual artery in the 15.38%; innervation was granted by the trigeminal system (buccal nerve and mylohyoid nerve), sometimes (46.15%) with hypoglossal component. CONCLUSIONS: These data suggest us to not consider myloglossus as a rare anatomical variant.

Symmetrical anatomical variant of the anterior belly of the digastric muscle: clinical implicat.

The digastric muscle is an important surgical landmark. Several anatomical variants of the digastric muscle are reported in literature and, in particular, the presence of accessory anterior bellies of the muscle is not uncommon. Here, an unreported symmetrical variant of the digastric muscle was found during a dissection of the suprahyoid region. The dissection showed digastric muscles with an accessory anterior belly, which originated from the anterior belly of muscles in proximity and anteriorly to the intermediate tendon. The accessory bellies were fused together on the midline and were attached with a unique tendon to the inner surface of the mental symphysis. These muscles completely filled the submental triangle. This unreported anatomical variant could be considered an additional contribution to description of the anatomical variants of the digastric muscle, with several implications in head and neck pathology, diagnosis and surgery.

Attenuation of ultraviolet A-induced alterations in NIH3T3 dermal fibroblasts by melatonin.

BACKGROUND: Sun exposure is responsible for long-term clinical skin changes such as photoageing, photodamage and photocancers. Ultraviolet (UV)A wavelengths stimulate the production of reactive oxygen species (ROS) that may contribute to photoageing. To protect against oxidative stress, skin cells have developed several defence systems, including ROS and metal ion scavengers and a battery of detoxifying, haem-degrading and repair enzymes. Melatonin's antioxidant activity is the result of three different but complementary actions: (i) a direct action due to its ability to act as a free radical scavenger; (ii) an indirect action that is a consequence of melatonin's ability to reduce free radical generation (radical avoidance); and (iii) its ability to upregulate antioxidant enzymes. OBJECTIVES: In this study, we focused our attention on the prevention of photodamage, choosing melatonin as an antioxidant agent. METHODS: In the present study we analysed the effects of pretreatment of murine fibroblasts cells (NIH3T3) with melatonin (1 mmol L(-1) ) followed by UVA irradiation (15 J cm(-2) ). Thereafter, changes in components of the extracellular matrix and in some antioxidant enzymes (inducible and constitutive haem oxygenase) were evaluated. RESULTS: We observed that UVA radiation caused altered expression of extracellular matrix proteins and induced the expression of inducible haem oxygenase. This increase was not sufficient to protect the cells from damage. Instead, melatonin pretreatment led to increased expression of haem-degrading enzymes and suppression of UVA-induced photodamage. CONCLUSIONS: These results suggest that melatonin, as a modifier of the dermatoendocrine system, may have utility in reducing the effects of skin ageing.

A randomized, double-blind, placebo- and active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common autoimmune condition, causing inflammation-induced hair loss. This disease has very limited treatment possibilities, and no treatment is either curative or preventive. Platelet-rich plasma (PRP) has emerged as a new treatment modality in dermatology, and preliminary evidence has suggested that it might have a beneficial role in hair growth. OBJECTIVES: To evaluate the efficacy and safety of PRP for the treatment of AA in a randomized, double-blind, placebo- and active-controlled, half-head, parallel-group study. METHODS: Forty-five patients with AA were randomized to receive intralesional injections of PRP, triamcinolone acetonide (TrA) or placebo on one half of their scalp. The other half was not treated. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. Patients were followed for 1 year. RESULTS: PRP was found to increase hair regrowth significantly and to decrease hair dystrophy and burning or itching sensation compared with TrA or placebo. Ki-67 levels, which served as markers for cell proliferation, were significantly higher with PRP. No side-effects were noted during treatment. CONCLUSIONS: This pilot study, which is the first to investigate the effects of PRP on AA, suggests that PRP may serve as a safe and effective treatment option in AA, and calls for more extensive controlled studies with this method.

Apolipoprotein E deficiency and a mouse model of accelerated liver aging.

The liver is the central metabolic organ which regulates several key aspects of lipid metabolism. The liver changes with age leading to an impaired ability to respond to hepatic insults and an increased incidence of liver disease in the elderly. Apolipoprotein E (ApoE) null mice have proved to be a very popular model to study spontaneous atherosclerosis, but recently it has been demonstrated that in ApoE-/- mice liver there are enzymatic and structural alterations, normally linked to the age. The purpose of this study was to consider ApoE-/- mice as a model for oxidative stress induced hepatic disease and to clarify how ApoE inactivation accelerates the aging process and causes liver disease.We used ApoE null mice and control mice at different ages (6 weeks and 15 months).Liver morphological damage as well as proteins involved in oxidative stress and liver ageing were all analyzed.Our study showed that ApoE null mice develop important age-related changes including oxidative stress, pseudocapillarization, increased polyploidy, decreased hepatocyte number and increased nuclear size. Our findings provide evidence that hypercholesterolemic ApoE-/- mice are more likely to develop severe liver injury, suggesting that in addition to vascular disease, increased cholesterol products and oxidative stress may also play a role in accelerating the progression of aging in the liver.

Osteonecrosis of the jaws and bevacizumab therapy: a case report.

Bevacizumab is a humanized recombinant monoclonal antibody that blocks vascular endothelial growth factor (VEGF). Recently, its use has been related with osteneocrosis of the jaws (ONJ), a disease showing a histological pattern similar to bisphosphonate-related ONJ. The aim of this study is to describe an ONJ case-report following bevacizumab chemotherapy without bisphosphonate therapy. We monitored ONJ development associated with the use of bevacizumab in a 47-year-old male with primitive adenocarcinoma of the parotid gland. Our results could suggest a possible correlation between the eruption of the lower third molar tooth and ONJ development following bevacizumab therapy. Clinicians should be aware of the potential risk of bevacizumab-related ONJ complication; moreover, since there are no effective therapeutic protocols for ONJ treatment, it is very important that patients develop good oral hygiene habits and undergo regular dental status evaluation by dentists.

Metabolic syndrome and chronic simvastatin therapy enhanced human cardiomyocyte stress before and after ischemia-reperfusion in cardio-pulmonary bypass patients.

Metabolic syndrome (MetS) is a set of metabolic alterations including high levels of low-density lipoprotein (LDL), which increase the risk of cardiomyopathy often leading to surgery. Despite inducing myopathy, statins are widely used to lower LDL. Cardiopulmonary bypass (Cpb) causes oxidative stress and metabolic injury, altering mitochondrial expression (Grp75) and endoplasmic reticulum (Grp78) chaperones, apoptotic enzymes (Bcl2 family) and increasing cardiomyocyte lipid/lipofuscin storage. We believe that cardiomyocytes from patients with MetS may be more sensitive to surgical stress, in particular after simvastatin therapy (MetS+Stat). The study group included ten patients with MetS, ten patients with Mets+Stat and ten healthy subjects. Myocardial biopsies were obtained both before and after-Cpb. Grp75, Grp78, Bax, Bcl2, lipids, lipofuscin and fibrosis were evaluated by immuno/histochemistry. MetS cardiomyocytes had higher Grp75, Bax, fibrosis and lipofuscin. MetS+Stat had lower Grp75 and higher Grp78 expressions, high Bax, fewer fibrosis and higher lipofuscin content. Cpb did not vary the fibrosis and lipids/lipofuscin content, although it influenced the chaperones and Bax expression in all groups. These changes were more profound in patients with MetS and even more so in patients with MetS+Stat. The results suggest that MetS and MetS+Stat cardiomyocytes were more highly stressed after-Cpb. Interestingly, simvastatin caused high stress even before-Cpb.

Role of apolipoprotein E in renal damage protection.

It is well-known that nephrotic syndrome and chronic renal failure are associated with lipid and lipoprotein abnormalities. For a long time, it has been thought that hyperlipidemia is a secondary and insignificant condition of these renal injuries. Recently, it has been shown that dyslipidaemia may contribute to the development and progression of chronic kidney disease. Apolipoprotein E (apoE) null mice are a very popular model for studying spontaneous hypercholesterolemia, but only limited data are available for the role of apolipoprotein E in kidney disease. The purpose of this study is to evaluate kidney disease in apolipoprotein E deficient mice. For this study, apoE null mice and control mice at different ages (6 weeks and 15 months) were used. Kidney morphological damage and proteins involved in oxidative stress and aging (TNF-α and NF-kB) were analyzed. ApoE deficient mice have morphological alterations that are the hallmark of kidney pathogenesis, which increase with the age of the animals. In apoE null mice kidneys, there is also increased oxidative stress as compared to control mice at the same age and fewer antioxidant enzymes. Our findings add to the growing list of protective effects that apoE possesses.

Essential amino acid supplementation decreases liver damage induced by chronic ethanol consumption in rats.

The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20 percent EtOH (the EtOH group), or drinking water with 20 percent EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage.

Beneficial effects of melatonin on nicotine-induced vasculopathy.

Tobacco smoking is responsible for death of many people each year and increases the risk of developing numerous disorders, particularly cardiovascular disease and cancer. Among the components of cigarette smoke, nicotine is known to excert proatherosclerotic, prothrombotic and proangiogenic effects on vascular endothelial cells. The current study was designed to investigate the mechanisms by which nicotine induces endothelial dysfunction and further to examine whether melatonin protects against nicotine-induced vasculopathy. Four groups of male rats (controls, melatonin-treated, nicotine treated [100 microg/mL in drinking water], and nicotine plus melatonin [5 mg/kg/day] treated) were used in this study. After 28 days all the animals were killed by decapitation and the aorta was removed. We evaluated the hydroxyproline content, and the different expression of proteins involved in several types of stress (ERK1/2), in fibrosis (TGF-beta1, NF-kappaB) and in recruitment of circulating leukocytes onto the vessel wall, including intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1). These metabolic pathways are important in the development of nicotine-induced atherosclerosis and hypertension. Our results show that nicotine induces marked structural and functional alterations in the aorta. Nicotine receptor binding results in activation and phosphorylation of ERK 1/2. This enzyme, in turn, activates both TGF-beta1 and NF-kappaB; they stimulate respectively the synthesis of type I collagen, responsible of fibrosis, and moreover ICAM-1, VCAM-1 and reactive oxygen species. Based on these findings, melatonin is able to minimize the negative effects of nicotine by blocking the activation of ERK and the other signalling pathways in which this enzyme is involved.

Supplementation with essential amino acids in middle age maintains the health of rat kidney.

Chronic kidney diseases are a social and economic problem, and diet has long been recognized as a fundamental modulator of kidney health in human and experimental models. Age-dependent alterations in mitochondrial function play a crucial role in the development of diseases of aging, and mitochondrial disorders have been observed in experimental models of kidney failure. Recently, the beneficial dietary effect of a specific mixture of essential amino acids (EAA) has been studied in elderly subjects, but no data were collected from the kidney. The aim of this study was to assess whether daily supplementation of the diet with EAA at the beginning of senescence could preserve renal health. We used middle-aged (18-month-old) male Wistar rats fed a standard diet and water ad libitum (M-aged group) or a diet with added EAA (1.5 g/kg per day) dissolved in drinking water for 3 months (M-aged+EAA group). Young (2-month-old) rats fed a standard diet for 3 months were used as controls. Mitochondrial morphology and markers for collagen, cyt-c-oxidase, HSP60, GRP75, eNOS, iNOS, Bax, Bcl2 and VEGF were analyzed in glomeruli and tubules. EAA supplementation limited fibrosis and increased the capillary tuft area in the glomeruli of M-aged rats. VEGF and eNOS were enhanced in glomeruli and the peritubular space with the EAA-supplemented diet. Mitochondrial cyt-c oxidase, Bcl2, and chaperones increased in the distal tubules of the EAA group to levels similar to those observed in the young group. Mitochondrial area and density after EAA intake did not differ from young groups. The results suggest that prolonged EAA intake could represent a strategy for maintaining the healthy status of the kidney in M-aged animals.

Intraosseous anastomosis in the maxillary sinus.

AIM: During sinus-lift surgery, certain intra-osseous vessels may be accidentally cut and this cause bleeding complications in approximately 20% of osteotomies. Therefore, understanding vascular details of the maxilla is very important for the surgeon. Here, we have given an anatomical overview of maxillary sinus vascularization through anatomical dissection. We have analyzed the distribution, localization and distance from the alveolar ridge of intraosseous branches of the maxillary artery found during sinus lift surgery. METHODS: Fifty-six maxillary bone doors were made bilaterally in twenty-eight unfixed cadavers; the doors were made between the first molar and the second molar (24 doors) or between the first and the second premolar (32 doors). RESULTS: Intraosseous arteries were found in 37 maxillary bones (66%). The average height of the artery from the alveolar crest was 13+/-3.2 mm in the distal doors and 18 +/- 6.1 mm in the mesial doors. Generally, the intraosseous maxillary branches ran caudo-rostrally; but in five maxillae, we found two parallel arteries, while in three cases the maxillary artery ran vertically. No differences were found between the left and right side. CONCLUSION: The risk of vascular damage in sinus floor elevation surgery is a real problem for the oral surgeon. Detailed anatomical knowledge about sinus vascularization is very important to reduce the risk of vascular damage and bleeding. In addition the visualization of sinus anastomosis by radiology and less invasive surgery, such as piezo-surgery, could be helpful.

In vitro effects of concentrated growth factors (CGF) on human SH-SY5Y neuronal cells.

OBJECTIVE: The aim of this study was to test the in vitro differentiation effects of concentrated growth factors (CGF), a platelet rich preparation, using SH-SY5Y cells, derived from human neuroblastoma. MATERIALS AND METHODS: SH-SY5Y cells were cultured in presence of CGF or retinoic acid (RA). After 72 h of treatment, different parameters were investigated: cell proliferation by an automated cell counter; cell viability by thiazolyl blue tetrazolium bromide (MTT) assay; cell differentiation markers, i.e., neuronal nuclear antigen (NeuN), synaptophysin (SYP) and ß3-tubulin, by immunocytochemistry and Western blotting techniques; release of nerve growth factor (NGF) and brain-derived growth factor (BDNF) by enzyme-linked immunosorbent assay (ELISA) and neurite outgrowth by a dedicated image software. RESULTS: In presence of CGF, the cell proliferation rate and viability decreased, as expected for differentiated SH-SY5Y cells. On the contrary, the cellular differentiation markers increased their expression together with the release of growth factors. Moreover, the neurite outgrowth was improved. CONCLUSIONS: The data suggest that CGF treatment positively affects the cell differentiation, regulating the expression of neuronal markers, the release of growth factors and the neurite length. Taken together these results seem to be promising in the development of new approaches for neural regeneration.

Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells.

BACKGROUND: In endothelial cells, caveolin-1, the structural protein of caveolae, acts as a scaffolding protein to cluster lipids and signaling molecules within caveolae and, in some instances, regulates the activity of proteins targeted to caveolae. Specifically, different putative mediators of the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation are located in caveolae and/or regulated by the structural protein caveolin-1, such as potassium channels, calcium regulatory proteins, and connexin 43, a molecular component of gap junctions. METHODS AND RESULTS: Comparing relaxation in vessels from caveolin-1 knockout mice and their wild-type littermates, we observed a complete absence of EDHF-mediated vasodilation in isolated mesenteric arteries from caveolin-1 knockout mice. The absence of caveolin-1 is associated with an impairment of calcium homeostasis in endothelial cells, notably, a decreased activity of Ca2+-permeable TRPV4 cation channels that participate in nitric oxide- and EDHF-mediated relaxation. Moreover, morphological characterization of caveolin-1 knockout and wild-type arteries showed fewer gap junctions in vessels from knockout animals associated with a lower expression of connexins 37, 40, and 43 and altered myoendothelial communication. Finally, we showed that TRPV4 channels and connexins colocalize with caveolin-1 in the caveolar compartment of the plasma membrane. CONCLUSIONS: We demonstrated that expression of caveolin-1 is required for EDHF-related relaxation by modulating membrane location and activity of TRPV4 channels and connexins, which are both implicated at different steps in the EDHF-signaling pathway.

Red wine polyphenols prevent cyclosporine-induced nephrotoxicity at the level of the intrinsic apoptotic pathway.

Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether Provinols flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with Provinols, or with CsA and Provinols simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. Provinols restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms.

PPADS, a purinergic antagonist reduces Fos expression at spinal cord level in a mouse model of mononeuropathy.

Recent evidence suggest that ATP plays a role as an endogenous pain mediator generating and/or modulating pain signaling from the periphery to the spinal cord. In this study we evaluated the effects of intraperitoneal administration of P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), evaluating pain related behaviours and monitoring the expression of Fos, a marker of activated neurons, in an experimental mouse model of neuropathic pain (sciatic nerve tying). The PPADS administration decreased both tactile allodynia and thermal hyperalgesia in a time and dose dependent manner. The dose of 25 mg/kg PPADS completely reversed nociceptive hypersensitivity. Moreover, non-noxious stimulation induced an increase of Fos positive neurons in the spinal cord of animals with tying of sciatic nerve. PPADS administration partially reversed this increase. These results suggest that PPADS reduces neuronal activation at spinal cord level and that P2 receptors are involved in the retrograde signalling progress exciting sensory spinal neurons.

Role of carbon monoxide and biliverdin in renal ischemia/reperfusion injury.

Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin/bilirubin with a concurrent release of iron. There is strong evidence that HO activity and products play a major role in renoprotection, however the exact molecular mechanisms underlying the beneficial effects exerted by this pathway are not fully understood. This review is aimed at illustrating the possible mechanism/s by which HO is renoprotective in the context of ischemia/reperfusion. We will first analyze the effects of exogenous administration of bilirubin/biliverdin and CO and then describe their biological activities once generated endogenously following stimulation of the HO pathway by either pharmacological means or gene targeting-mediated approaches.

Beneficial effects of Provinols: cardiovascular system and kidney.

Red wine polyphenols have been reported to exert beneficial effects in preventing cardiovascular diseases but their molecular mechanisms of hemodynamic effects on functional cardiovascular and renal changes were studied much less. The review is focused on in vitro as well as in vivo effects of red wine extract containing polyphenolic compounds (Provinols) on cardiovascular systems and kidney in relation to the molecular and biochemical mechanisms of these compounds. This review provides the evidence that Provinols is able to produce ex vivo endothelium-dependent relaxation as a result of enhanced NO synthesis. Administration of Provinols partially prevents the development of hypertension during NO deficiency and accelerates the decrease of blood pressure in already established hypertension. The effects of Provinols include prevention and/or attenuation of myocardial fibrosis, reduction of aortic wall thickening and improvement of vascular functions. These functional and structural alterations are associated with significant augmentation of NO production, seen as the increase of NO synthase activity and eNOS protein expression. Moreover, it has been documented that Provinols decreased the oxidative stress within the cardiovascular system and kidney.

HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions.

Five specimens of normal mammary tissue and 53 primary breast carcinoma lesions were tested for expression of HLA antigens and components of the antigen-processing machinery by immunohistochemical staining. The expression of transporter associated with antigen processing (TAP) 1, TAP2, and HLA class I antigens in breast carcinoma lesions was significantly associated with tumor grading. Like normal mammary tissue, the 16 low-grade (G1) breast carcinoma lesions showed strong staining for TAP1, TAP2, and HLA class I antigens. In contrast, only 12 (32%) of 37 high-grade (G2 and G3) breast carcinoma lesions displayed the normal staining pattern. In 14 (38%) of 37 high-grade lesions, HLA class I antigen down-regulation was observed without loss of low molecular mass polypeptide and/or TAP staining. Congruent down-regulation of HLA class I antigen and TAP1 or TAP2 was found in 8 (22%) of 37 high-grade lesions. Complete loss of HLA class I antigens, TAP1, and TAP2 was observed in 3 (8%) of 37 high-grade lesions. No lesion was negative for TAP1 and/or TAP2 staining while positive for HLA class I antigen staining. These data demonstrate an association of HLA class I antigen and TAP down-regulation with tumor progression in breast carcinoma. This association suggests that loss of HLA and/or TAP may represent an escape from the host's immune pressure or may reflect the accumulation of abnormalities associated with neoplastic progression. This accumulation of defects in antigen processing and presentation may in turn be responsible for reduced recognition of malignant cells by putative clinically relevant tumor-specific T cells.

The protective effect of caffeic acid phenethyl ester against cyclosporine A-induced cardiotoxicity in rats.

Cyclosporine A (CsA) is the immunosuppressor, which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been considered as one of the possible mechanisms of CsA-induced cardiotoxicity. The present investigation examines the ability of caffeic acid phenethyl ester (CAPE), which is an active component of propolis extracts, as a natural antioxidant to protect against CsA-induced oxidative stress and cardiotoxicity. CsA cardiotoxicity was induced by subcutaneous injection of CsA at a dose of 15 mg/kg/body weight daily for 21 days in rats. Cardiotoxicity was evaluated by morphological and biochemical studies. CsA treated rats showed degenerative changes with cardiac fibrosis localized around the fibers. These latters were disorganised and the network was disappeared. The ROS production was increased whereas cytochrome-c-oxidase decreased. The expression and levels of matrix metalloproteinase 2 (MMP2) were increased whereas those of its inhibitor were downregulated. CAPE subcutaneous administration (15 micromol/kg/day) improved cardiac cytoarchitecture, decreased the levels and the expression of MMP2, and increased those of TIMP2 proteins. Moreover, it increased cytochrome-c-oxidase activity and decreased ROS production. These results suggest that CAPE could have protective effect against CsA-induced cardiotoxicity.