Anti-Tumor Effect of the Ketogenic Diet against DMH-Induced Colon Cancer in Rats.

Colon cancer is one of the most common malignancies with significant importance. Recent theories believe that cancers are metabolic diseases. Therefore, the role of metabolism in the prevention and treatment of cancer has been considered and the ketogenic diet is one example. In the present study, we evaluated the effect of the ketogenic diet and a high carbohydrate diet on tumor size and number, histopathology, and insulin level as well as VEGF level in 1, 2 dymethylhydrazine (DMH)-induced colon cancer in rats. Forty adult male Wistar rats were divided into four groups as follows: control, colon cancer, ketogenic diet, and high carbohydrate diet groups. For induction of colon cancer, 30 mg/kg of 1,2 DMH solution was injected subcutaneously twice a week for 24 weeks. The results showed that the ketogenic diet reduced tumor size, number, and histopathological changes as well as VEGF level (P<0.01) compared to the colon cancer group. The ketogenic diet also increased the levels of beta hydroxyl butyrate (P<0.001) and decreased those of glucose, insulin and HbA1c (P<0.001). Furthermore, a high carbohydrate diet did not show any protective effects on colon cancer prevention. In conclusion, the ketogenic diet demonstrated prophylactic effects on colon cancer, and this anti-cancer effect could be partially attributed to the reduction in VEGF and insulin levels.

Effect of moderate exercises and curcumin on hepatic transcriptional factors associated with lipid metabolism and steatosis in elderly male rat.

BACKGROUND AND PURPOSE: The specific molecular mediators involved in dyslipidemia in older people are not yet clearly understood. The current study was, thus, an attempt to investigate whether moderate aerobic exercises and curcumin administration alleviates the abnormalities caused by aging in the rats' liver. EXPERIMENTAL APPROACH: Thirty-two eight-year-old young rats were classified into five groups, namely, young control, aged control, aged-curcumin, aged-exercise, and aged-curcumin-exercise co-treatment. The rats in the exercise groups were trained on an animal treadmill for 60 min/day five times per week for eight weeks. FINDINGS/RESULTS: The results revealed a significant increase in FAT/CD36, PTP1B, significantly decreased HNF4α genes expression, increase in LDL and cholesterol in the aged group compared to the young control. Compared to those in the young control group, no significant changes in HDL and TG amounts in the aged control were observed. Moreover, compared to the young control, the aged group showed liver histological changes such as fibrosis and mild or grade 1 steatohepatitis. Moderate aerobic exercise and curcumin alone or in combination completely masked this effect. CONCLUSION AND IMPLICATIONS: The findings revealed dyslipidemia and liver steatosis related to aging might be partly associated with changes in hepatic transcriptional factors which can be mitigated via moderate aerobic exercise and curcumin.

The protective effect of zinc on morphine-induced testicular toxicity via p53 and Akt pathways: An in vitro and in vivo approach.

BACKGROUND: Chronic use of morphine is associated with reproductive complications, such as hypogonadism and infertility. While the side effects of morphine have been extensively studied in the testis, much less is known regarding the effects of morphine on Sertoli cells and the effects of zinc on morphine-induced testicular injury as well as their underlying mechanisms. Therefore, the purpose of this study was to investigate the effect of morphine (alone and co-administered with zinc) on cell viability and apoptosis of the testicular (Sertoli) cells as well as the tumor suppressor p53 and phosphorylated-protein kinase B (p-Akt) protein levels in both in vitro and in vivo models. METHODS: Cultured Sertoli cells were exposed to morphine (23 µM), zinc (8 µM), and zinc prior to morphine and their effects on Sertoli cell viability and apoptosis were investigated. Morphine (3 mg/kg) and zinc (5 mg/kg, 1 h before morphine) were also injected intraperitoneally to rats and then the apoptotic changes in the testis were evaluated. RESULTS: Cell viability and p-Akt protein levels decreased in morphine-treated cells, while apoptosis and p53 protein expression increased in these cells. Pretreatment with zinc recovered morphine-induced apoptotic effects, as well as over-expression of p53 and down-regulation of p-Akt. These findings were supported by a subsequent animal study. CONCLUSION: The present data indicated the protective effect of zinc against morphine-induced testicular (Sertoli) cell toxicity via p53/Akt pathways in both in vivo and in vitro models and suggested the clinical importance of zinc on infertility among chronic opioid users and addicted men.

In Vitro and In Vivo Pretreatment with Selenium Mitigates Tetrahydrocannabinol-Induced Testicular Cell Apoptosis: the Role of AKT and p53 Pathways.

Exocannabinoids such as tetrahydrocannabinol (THC) may alter the physiological function of endocannabinoids in male reproduction and thus affect male fertility. This study aimed to investigate the apoptotic effects of THC via mechanisms related to p53 and AKT signaling pathways on Sertoli cells and seminiferous germinal cells, as well as the possible protective role of selenium pretreatment in both in vitro and in vivo models. The Mus musculus Sertoli cell line, TM4, was used for in vitro experiments. The TM4 cells were cultured and exposed to selenium (2 µM, 48 h) and THC (470 µM, 24 h). The MTT test was performed to evaluate cell viability. Fifteen male Wistar rats (220 ± 20 g) were used for in vivo experiments and divided into three groups: (1) control, (2) tetrahydrocannabinol (THC, 5 mg/kg, dissolved in DMSO 5%, i.p., for 21 consecutive days), and (3) THC + selenium (selenium, 0.5 mg/kg per day, i.p.). At the end of the experiments, Sertoli cells and testis tissue samples were collected for biochemical (AKT, P53), cell apoptosis, and histological analyses. The results of the in vitro study revealed that THC significantly decreases the cell viability (p < 0.001) and expression of the p-AKt protein (p < 0.05) and increases Sertoli cells' apoptosis (p < 0.001) and p53 protein expression (p < 0.001). The in vivo effects of THC were in line with the in vitro results. Pretreatment with selenium (as sodium selenite) significantly decreased the THC-induced Sertoli cell and testicular tissue damages in the rats. Pathological changes were significantly alleviated in the selenium-pretreated rats. Collectively, these data suggest that pretreatment with selenium is able to protect against THC-induced testicular cell damage. The attenuating effect of selenium may be due to its anti-apoptotic activity through the p53 and AKT modulation.

Schwannoma and Neurofibroma, Originating from the Ulnar Nerve in Neurofibromatosis: A Case Report and Review of the Literature.

Schwannomas and neurofibromas are rare benign tumors originating from the peripheral nerve sheath. Tumors in neurofibromatosis are mostly neurofibromas and often appear in the soft tissue of peripheral nerves. In this report, a patient presented with two large adjacent soft tissue tumors in the right wrist and distal forearm which originated from a common nerve. A schwannoma had formed beside a neurofibroma from the ulnar nerve and induced numbness and paresthesia in the little and ring fingers. Although the patient had café au lait spots on the skin, neurofibromatosis was not suspected due to lack of symptoms. The patient was referred to the current research clinic suffering from two soft tissue masses in the wrist and ulnar nerve dysfunction. In neurofibromatosis patients, two tumors of a different nature originating from a common nerve close together have rarely been described in the literature. The patient was treated by en bloc excision of the mass while protecting the nerve fascicles. The follow-up results indicated no neurological symptoms and complete restoration of ulnar nerve function.

Cyclosporine A induces kidney dysfunction by the alteration of molecular mediators involved in slit diaphragm regulation and matrix metalloproteins: the mitigating effect of curcumin.

BACKGROUND: This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. METHODS: Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. RESULTS: A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. CONCLUSION: Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.

Protective effect of curcumin on fertility of rats after exposure to compact fluorescent lamps: An experimental study.

BACKGROUND: Testicular function is modified by maturational gonadostatic control highly susceptible to negative physiologic niche-altering factors like UV-rays. OBJECTIVE: This study was performed in order to uncover new aspects of Compact Florescent Lamps (CFLs) induced damages on the testicular tissue of rats and evaluating the effect of curcumin on testis of rats after exposure to compact florescent Lamps. MATERIALS AND METHODS: Twenty-four adult male Albino rats were randomly divided into three groups: control group (ethyl oleate 0.2 ml, IP, for 45 days, without CFLs exposure), fluorescent group (ethyl oleate 0.2 ml, IP, daily and treated with 12 hr CFLs exposure for 45 days) and curcumin group (curcumin 20 µ M, IP along with 12 hr CFLs exposure for 45 days). The rats were anesthetized at the end of the experiment. Gonadotropin hormones and prolactin levels were measured; Histopathological and histomorphometrical analysis of the testis was carried out. RESULTS: Results of this study showed that CFLs significantly decreased serum levels of follicle stimulating hormone, prolactin, testicular weight, sperm motility, TDI, and SPI. Furthermore, CFLs had no effect on serum levels of luteinizing hormone and sperm count and also, increased abnormal sperm shapes. Our results also showed that curcumin supplementation following CFLs reversed these alterations. CONCLUSION: These results strongly suggest that CFLs severely impairs testis while curcumin as an antioxidant had protective effects on undesirable effects in testis induced by CFLs.

Systemic administration of curcumin nanoparticles protects ischemia-reperfusion injury in ovaries: An animal model study.

OBJECTIVE: Ovarian torsion must be diagnosed and treated as early as possible. The aim of the present study was to investigate the effects of intraperitoneal administration of nanocurcumin on ischemia-reperfusion injury in ovaries. METHOD: Thirty-five (35) healthy female Wistar rats weighing approximately 250 g were randomized into seven experimental groups (n=5): Group SSG - The rats underwent only laparotomy. Group I: A 3-hour ischemia only. Group I/R: A 3-hour ischemia and 3-hour reperfusion. Group I/C: A 3-hour ischemia only, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/NC: A 3-hour ischemia only and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. RESULTS: Nanocurcumin-treated animals showed significantly improved development of ischemia and reperfusion tissue injury compared to those in the other groups (p<0.05). Significant higher values of SOD, tGSH, GPO, GSHRd and GST were observed in I/R/NC animals compared to those in the other groups (p<0.05). The damage indicators (NOS, MDA, MPO and DNA damage level) were significantly lower in I/R/NC animal compared to those of other groups (p<0.05). CONCLUSION: Intraperitoneal administration of nanocurcumin can be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia.

Systemic administration of curcumin nanoparticles protects ischemia-reperfusion injury in ovaries: An animal model study

Summary Objective: Ovarian torsion must be diagnosed and treated as early as possible. The aim of the present study was to investigate the effects of intraperitoneal administration of nanocurcumin on ischemia-reperfusion injury in ovaries. Method: Thirty-five (35) healthy female Wistar rats weighing approximately 250 g were randomized into seven experimental groups (n=5): Group SSG - The rats underwent only laparotomy. Group I: A 3-hour ischemia only. Group I/R: A 3-hour ischemia and 3-hour reperfusion. Group I/C: A 3-hour ischemia only, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/NC: A 3-hour ischemia only and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. Results: Nanocurcumin-treated animals showed significantly improved development of ischemia and reperfusion tissue injury compared to those in the other groups (p<0.05). Significant higher values of SOD, tGSH, GPO, GSHRd and GST were observed in I/R/NC animals compared to those in the other groups (p<0.05). The damage indicators (NOS, MDA, MPO and DNA damage level) were significantly lower in I/R/NC animal compared to those of other groups (p<0.05). Conclusion: Intraperitoneal administration of nanocurcumin can be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia.

The Extract of Lycium depressum Stocks Enhances Wound Healing in Streptozotocin-Induced Diabetic Rats.

In diabetes, impaired wound healing and other tissue abnormalities are considered major concerns. The aim of the present study was to assess the wound-healing activity of methanolic extracts of the extract of Lycium depressum leaves. A total of 60 healthy male Wistar diabetic rats weighing approximately 160 to 180 g and 7 weeks of age were randomized into 10 groups for incision and excision wound models: sham surgery group (SHAM), including creation of wounds and no treatment; base formulation group (FG) with creation of wounds and application of base formulation ointment; treatment group 1 (TG1) with 1 g of powder extract of the plant material in ointment; treatment group 2 (TG2) with 2 g; and treatment group 4 (TG3) with 4 g of powder extract of the plant material in ointment. A wound was induced by an excision- and incision-based wound model in male rats. The mature green leaves of L depressum were collected and authenticated. Extractions of dried leaves were carried out. For wound-healing activity, the extracts were applied topically in the form of ointment and compared with control groups. The healing of the wound was assessed based on excision, incision, hydroxyproline estimation, and biomechanical and biochemical studies. The extract of L depressum leaves enhanced wound contraction, decreased epithelialization time, increased hydroxyproline content, and improved mechanical indices and histological characteristics in treatment groups compared with SHAM and FG ( P < .05). These findings permit the conclusion the extract of L depressum benefits parameters of wound healing in a diabetes induced model.

Evaluation of Ki67, p16 and CK17 Markers in Differentiating Cervical Intraepithelial Neoplasia and Benign Lesions.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histomorphologic diagnosis is subject to high rates of discordance among pathologists. The aim of this study was to evaluate Ki-67 (MIB-1), CK17 and p16 (INK4a) (p16) markers by immunohistochemical methods in differentiating CIN from benign cervical lesions. METHODS: The present study reviewed and re-classified 77 cervical biopsies, originally diagnosed as 31 non-CIN, and 46 CIN, as 54 non-CIN, and 23 CIN based on at least two similar diagnoses. Immunostaining by Ki67, p16 and CK17 markers was performed on all cases and the results were compared with pervious and consensus diagnosis. RESULTS: The overall agreement between pervious and consensus diagnosis was 67.5% (Kappa=0.39, P<0.001). The sensitivity and specificity of Ki67 immunostaining were 95.6% and 85.1% respectively, while for p16 the corresponding values were 91.3% and 98.1%. The overall agreement, for both p16 and Ki67, with consensus diagnosis were significant (P<0.001). The sensitivity and specificity of CK17 negative staining in CIN detection were 39.1% and 40.7% respectively. CONCLUSION: Ki67 and p16 markers are recommended as complementary tests for differentiating between dysplastic and non-dysplastic lesions. CK17 does not discriminate between immature metaplasia with and without dysplasia.