Crocin, the compound of the dried stigma of Crocus sativus L (saffron), restores doxorubicin-induced disturbances in kidney functioning, oxidative stress, inflammation, renal tissue morphology and TGF-ß signalling pathways.

Doxorubicin (Dox), an anthracycline antibiotic, is a chemotherapeutic drug for several cancer treatments. However, its clinical usage has been restricted because of severe side effects, including nephrotoxicity. This study aimed to demonstrate the possible nephroprotective effects of crocin (Cr) against Dox-induced oxidative stress, renal inflammation, renal morphology and transforming growth factor-ß (TGF-ß) signalling pathways in Dox-exposed rats. Hence, the rats were injected for 15 d consecutively with saline, six different injections of Dox until the cumulative dose reached 12 mg/kg., daily Cr (40 mg/kg), and Dox + Cr combination. Cr increased the activities of superoxide dismutase (SOD) and catalase (CAT), GSH content and suppressed inflammation and oxidative stress in Dox-exposed rats. Our results were confirmed by immunohistochemical findings that Cr treatment ameliorates the expressions of IL1ß and TGF-ß in Dox-induced nephrotoxicity. Conclusionally, Cr exhibits adequate nephroprotective effects against Dox-induced nephrotoxicity on rat kidney architecture and tissue function by stabilising cellular redox homeostasis, reducing renal fibrosis and suppressing inflammation.

Once upon a time in Anatolia: the kings with bulging eyes.

The Hittite Empire, formed by the Hittites who settled in central Anatolia at the beginning of the second millennium BC, has left behind rich archeological remains. In this historical review, statues of the Hittite priest-kings, King Idrimi, King Suppiluliuma, and King Tarhunza, who ruled in these lands in ancient times, are analyzed. Graves' disease (GD) is the most common cause of hyperthyroidism. Patients with GD are also at risk of developing Graves' orbitopathy (GO). Upper eyelid retraction and exophthalmos (bulging eyes) are common in patients diagnosed with GO. Could the kings who lived in Anatolia at different times in the distant past have suffered from the same disease?

The effects of pinealectomy and melatonin treatment in acrylamide-induced nephrotoxicity in rats: Antioxidant and anti-inflammatory mechanisms.

OBJECTIVE: Acrylamide (AA) is toxic and forms in food that undergoes high-temperature processing. This study aimed to investigate the effects of AA-induced toxicity on renal tissue in pinealectomized rats and the possible protective effect of exogenous Melatonin (ML) administration. MATERIALS AND METHODS: Sixty rats were randomized into 6 groups (n = 10): Sham, Sham+AA, Sham+AA+ML, PX, PX+AA, and PX+AA+ML. Sham and pinealectomized rats received AA (25 mg/kg/day orally) and ML (0.5 ml volume at 10 mg/kg/day, intraperitoneal) for 21 days. RESULTS: The results showed that malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) levels of the kidney and urea and creatinine levels of serum in the PX (pinealectomy)+AA group were more increased than in the Sham+AA group. In addition, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) levels decreased more in the PX+AA group than in the Sham+AA group. Also, we observed more histopathologic damage in the PX+AA group. On the other hand, up-regulation of kidney tissue antioxidants, down-regulation of tissue oxidants, and improvement in kidney function were achieved with ML treatment. Also, histopathological findings such as inflammatory cell infiltration, shrinkage of glomeruli, and dilatation of tubules caused by AA toxicity improved with ML treatment. CONCLUSION: ML supplementation exhibited adequate nephroprotective effects against the nephrotoxicity of AA on pinealectomized rat kidney tissue function by balancing the oxidant/antioxidant status and suppressing the release of proinflammatory cytokines.

Halil Pasha's legacy as a Turkish painter: Esotropia or pseudoesotropia in "Yasli Halayik".

Introduction: Esotropia is a form of strabismus, a condition characterized by the misalignment of the eyes. Specifically, esotropia refers to inward deviation of one or both eyes. It can manifest at different ages, ranging from infancy to adulthood, and can have varying degrees of severity. The false appearance of esotropia in the alignment of the visual axes is what defines pseudoesotropia. Halil Pasha was a Turkish painter known for his contributions to the art scene during the late 19th and early 20th centuries. His artistic talent, coupled with his influential position as a statesman, allowed him to leave a lasting impact on the cultural landscape of the Ottoman Empire. Methods: In the present study, artistic depictions of esotropia or pseudoesotropia in Halil Pasha's "Yasli Halayik" were evaluated. A comprehensive literature review on strabismus in medicine and art was conducted. Results: "Yasli Halayik", translated as "Old Servant Woman", is one of the iconic paintings of Turkish art. It reflects the social dynamics and lifestyle of the time, offering a glimpse into the lives of women serving in Ottoman households. When we examine this painting as a physician, the first thing we notice is the old woman's eyes. An eye misalignment in the left eye of the old servant woman is noticed. Discussion: In medical humanities, which are addressed in medical education, medicine and art intersect with different perspectives and understandings. Although the evaluation of medical scenes in artworks seems to have been first observed by an art historian, today physicians and medical students need to examine artworks more carefully and develop their observational skills. Iconodiagnosis is the medical analysis of artworks that looks for clinical signs suggestive of medical disorders and diseases. The application of iconodiagnosis in medical education is an alternative and stimulating way to exercise students' observation skills; not only the physical examination of the patient is important, but also the information obtained from their posture, clothing, general demeanour and even physical aids.

Cytotoxic effects of Phenformin on ovarian cancer cells: expression of HIF-1α and PDK1 in the hypoxic microenvironment.

Today, many anticancer drugs are used clinically for ovarian cancer, one of the leading causes of cancer-related deaths in women. Phenformin is an antidiabetic drug of the biguanide class. It improves the antiproliferative activity in cancer cells. Hypoxia is an important component associated with ovarian cancer and its tumor microenvironment. The aim of this study was to investigate the anticancer effects of Phenformin in SKOV-3 human ovarian cancer cells under hypoxic conditions. SKOV-3 human ovarian cancer cells treated with different doses of Phenformin (0.5 mM, 1 mM, 2 mM, 5 mM) for 24 hours were subjected to WST-1 cell viability assay and Annexin V apoptosis assay. A dose-dependent decrease in cell viability with Phenformin treatment was observed. In addition, Phenformin activated percentage of apoptotic SKOV-3 cancer cells in a dose-dependent manner. In this study, Cobalt(II) chloride (CoCl2) treatment leads to increased hypoxia-inducible factor-1alpha (HIF-1α) expression and Phenformin can recover hypoxic condition. HIF-1α protein expression was significantly correlated with cell viability assay and apoptosis assay. We also found that Phenformin inhibits expression of phosphoinositide-dependent kinase 1 (PDK1) in SKOV-3 ovarian cancer cells. The ability to migrate to cancer cells was significantly reduced in a dose-dependent manner with Phenformin. This data demonstrates that Phenformin treatment can induce apoptosis and inhibit proliferation in ovarian cancer cells under hypoxic conditions. The findings reveal that HIF-1α is a new target for the treatment of ovarian cancer.

Crocin treatment exerts anti-inflammatory and anti-oxidative effects in liver tissue damage of pinealectomized diabetic rats.

Diabetes mellitus (DM) is a chronic metabolic disorder with an increasing global prevalence that leads to significant morbidity and mortality. The liver plays a vital role in glycemic regulation in physiological and pathological conditions such as DM. Free radical formation and inhibition of antioxidant defense systems play a role in the liver damage pathogenesis in diabetic patients The antioxidant, anti-diabetic, anti-inflammatory, and radical scavenging properties of crocin are known. This study was designed to determine the possible protective effects of crocin against liver tissue damage in pinealectomized diabetic rats. Sixty rats were divided into six groups: Control, Sham+streptozotocin (STZ), Pinealectomy (PINX), PINX+STZ, PINX+Crocin, and PINX+STZ+Crocin. PNX procedure was carried out on the first day of the experiment. Intraperitoneal (i.p.) injection of 50 mg/kg STZ was performed on the 30th day of the experiment to induce DM. Crocin (50 mg/kg; i.p.) was applied for 15 days after the pinealectomy procedure and induction of DM. Crocin decreased the markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin-1ß (IL-1ß), and malondialdehyde (MDA)) of liver damage and increased antioxidant enzyme levels and tissue total antioxidant status. Histological results showed that the administration of crocin exhibited a protective effect against liver damage caused by STZ. These results indicate that crocin evidence protection against liver injury caused by STZ.

Therapeutic role of melatonin on acrylamide-induced hepatotoxicity in pinealectomized rats: Effects on oxidative stress, NF-κB signaling pathway, and hepatocellular proliferation.

Acrylamide (AA) is formed in some foods by the cooking process at high temperatures, and it could be a carcinogen in humans and rodents. The purpose of the current study was to reveal the possible protective effects of melatonin against AA-induced hepatic oxidative stress, hepatic inflammation, and hepatocellular proliferation in pinealectomized rats. Hence, the sham and pinealectomized rats were consecutively given AA alone (25 mg/kg) or with melatonin (10 mg/kg) for 21 days. Melatonin acts as an antioxidant, anti-inflammatory, and antiapoptotic agent and introduces as a therapeutic strategy for AA-induced hepatotoxicity. Melatonin supplementation reduced AA-caused liver damage by decreasing the serum AST, ALT, and ALP levels. Melatonin raised the activities of SOD and CAT and levels of GSH and suppressed hepatic inflammation (TNF-α) and hepatic oxidative stress in liver tissues. Moreover, histopathological alterations and the disturbances in immunohistochemical expression of NF-κB and Ki67 were improved after melatonin treatment in AA-induced hepatotoxicity. Overall, our results demonstrate that melatonin supplementation exhibits adequate hepatoprotective effects against hepatotoxicity of AA on pinealectomized rat liver architecture and the tissue function through the equilibration of oxidant/antioxidant status, the regulation of cell proliferation and the suppression of the release of proinflammatory cytokines.

Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by α-naphthylthiourea.

We aimed to observe the possible effects of melatonin (MLT) deprivation (pinealectomy) and exogenous MLT administration on pulmonary edema induced by alpha-naphthylthiourea (ANTU), a toxic chemical agent, in rats. Seventy animals were assigned to seven groups: control, sham pinealectomy (PINX), PINX, ANTU (10 mg/kg intraperitoneal on day 30), ANTU + MLT (10 mg/kg/day i.p. for 30 days), ANTU + PINX, and ANTU + PINX + MLT.In this study, pleural effusion (PE) formation, lung weight/body weight (LW/BW) and PE/BW ratios (fluid accumulation and weight values in the lungs) increase detected. Pre-ANTU MLT administration led to significant decreases in PE, LW/BW, and PE/BW levels. The inhibited glutathione (GSH) and superoxide dismutase (SOD) levels and high malondialdehyde (MDA) levels that ANTU increase lipid peroxidation in the study. MLT administration eliminated oxidative stress by reducing MDA and ameliorating GSH and SOD levels.Pre-ANTU MLT administration led to a significant decrease in interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels in the lung when compared to the ANTU group without MLT administration. Post-pinealectomy ANTU administration significantly increased IL-1ß and TNF-α levels when compared to ANTU and MLT administration without pinealectomy. Diffused inflammatory cell infiltration, interstitial pulmonary edema, and histopathological congestion were observed after the administration of ANTU. Severity of the damage was elevated in the ANTU + PINX group. MLT treatment regressed pulmonary effusion and edema and improves lung structure. In brief, the findings suggested that MLT inhibited proinflammatory mediators and could serve as a therapeutic agent to prevent inflammatory disorders.

Evaluation of the usage of YouTube videos about Histology and Embryology as an educational material.

The use of YouTube videos for educational purposes has been increasingly popular. The quality and accuracy of the information level of these videos should be checked by expert trainers. This study aims to evaluate the content, quality and functionality of YouTube videos on Histology and Embryology and to measure their educational usefulness. In the study, searches were performed using the keywords "Histology" and "Embryology" in the YouTube search tab. Quality and content were evaluated using the Video Power Index (VPI), modified DISCERN scale, JAMA and the Global Quality Scale (GQS). Videos were categorized by educational usefulness. SPSS software was used for statistical analysis. A statistically significant high correlation was observed between modified DISCERN scores and JAMA scores (r = 0.757, p < 0.001) and between modified DISCERN scores and GQS scores (r = 0.743, p < 0.001). A statistically significant high correlation was also determined between JAMA and GQS scores (r = 0.632, p < 0.001). GQS scores were weakly, negatively and significantly correlated with the number of comments (r = -0.302, p < 0.05) and dislikes (r = -0.325, p < 0.05). Based on GQS, the useful and non-useful videos differed significantly in terms of views, likes, dislikes, comments counts and days since upload (p < 0.05). Modified DISCERN and JAMA scores also differed significantly between the useful and non-useful videos (p < 0.001). Educational videos published for Histology and Embryology education on the internet will be more beneficial if they are prepared by expert educators from reliable information sources, by the current literature, and by scoring systems such as DISCERN, JAMA and GQS.

Synovial fluid niche promoted differentiation of dental follicle mesenchymal stem cells toward chondrogenesis in rheumatoid arthritis.

Objectives: In this study, we aimed to investigate the differentiation potential of dental follicle mesenchymal stem cells (MSCs) in the synovial fluid (SF) niche of early-onset or end-stage rheumatoid arthritis (RA). Patients and methods: Between May 2020 and January 2021, six patients (1 male, 5 females; mean age: 57.5±11.2 years; range, 49 to 65 years) who were diagnosed with RA with the indication of SF aspiration were included in the study. The third passage dental follicle stem cells (DFSCs) were cocultured with fresh SF samples of end-stage or early-onset RA patients in micromass culture system for 21 days. SF samples were analyzed for secreted cytokines. Chondrogenic markers (CD49e, CD49f) were analyzed in DFSCs, gene expression analysis was performed for the expressions of Col I, Col II, Aggrecan and Sox-9, and histochemical analysis was performed by staining three-dimensional pellets with anti-collagen II antibody. The neutralization assay was performed with anti-interleukin (IL)-6, anti-interferon-gamma (IFN-g), and anti-IL-1beta(b). Results: The high levels of IL-1b and IL-6 were observed in end-stage RA patients' SF samples compared to the early-onset patients (p<0.05). The CD49e and CD49f expressions in DFSCs were significantly higher in the SF samples of end-stage RA patients (p<0.05). Also, the Col II, Sox-9 and Aggrecan messenger ribonucleic acid (mRNA) expressions increased in the DFSCs, when cultured with end-stage RA patients' SF samples (p<0.01). Collagen-II expression in histochemical analysis of micromass pellets was higher in the DFSCs cultured with end-stage RA patients' SF samples. The neutralization of IL-6 significantly decreased the CD49e and CD49f expressions (p<0.05). Conclusion: The high levels of IL-6 in SF niche of end-stage RA patients were found to differentiate DFSCs toward chondrogenesis. Based on these findings, DFSCs can be used as a new cell-based treatment in RA patients for the cartilage damage.

Neuroprotection by melatonin against acrylamide-induced brain damage in pinealectomized rats.

The current study aimed to evaluate the neuroprotective effect of exogenous melatonin against acrylamide (ACR)-induced oxidative stress and inflammatory and apoptotic responses in the brain tissues in pinealectomized rats (PINX). ACR is a toxic chemical carcinogen that occurs owing to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. The rats who underwent pinealectomy and sham pinealectomy were exposed to ACR (25 mg/kg b.w., orally) alone or with exogenous melatonin (10 mg/kg b.w., i.p.) for 21 consecutive days. Alterations of brain oxidant/antioxidant status, dopamine (DA), Brain-Derived Neurotropic Factor (BDNF) inflammatory mediator and apoptosis during exposure to ACR in pinealectomized rats were more than without pinealectomized rats. Histopathological changes were more in brain tissue of pinealectomized rats after ACR administration. Exogenous melatonin treatment in ACR -exposed rats following pinealectomy increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS) compared to PINX+ACR. Moreover, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in ACR-intoxicated brain tissues. In addition, after exposure to ACR on pinealectomized rats, melatonin treatment ameliorated BDNF and DA levels in brain tissues. Furthermore, exogenous melatonin intervention in ACR-intoxicated rats significantly rescued the architecture of neuronal tissues. In summary, the present study, for the first time, suggested that exogenous melatonin treatment could reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological alterations in the brain tissue of pinealectomized rats after ACR administration.

Leptin Accelerates Endothelial Wound Healing: Role of Endothelial Nitric Oxide Synthase Expression.

BACKGROUND: The endothelium is crucial for the control of vascular homeostasis and plays a role in angiogenesis. Leptin, a protein released mainly by adipose tissue, plays a key role in the regulation of energy balance and angiogenesis. We aimed to investigate the changes of endothelial nitric oxide synthetase expression on human umbilical vein endo- thelial cells wound healing model after leptin treatment. METHODS: In this study, 5 groups were planned as Group 1: control (untreated), Group 2: treated with 0.1 ng/mL leptin, Group 3: treated with 1 ng/mL leptin, Group 4: treated with 10 ng/mL leptin, and Group 5: treated with 100 ng/mL leptin. Closure rates of wound areas were calculated by the Image J program after 24 hours of leptin treatment. The WST-1 assay was used to calculate the cell viability. Immunocytochemical analysis was performed for endothelial nitric oxide synthase expression and H-Score was calculated. RESULTS: The closure rates of wound areas were calculated as 80.24%, 89.73%, 87.40%, 90.73%, and 93.70%, respectively. When all groups treated with leptin were comparedwith the control group, there was a statistically significant difference (P < .05). The WST-1 results showed that the most increasing levels of viable cells were found in the groups treated with 0.1 ng/mL leptin and 100 ng/mL leptin when compared to the control group. H-Score values of each group were calculated as 284.8 ± 15.22, 288.6 ± 8.41, 291 ± 8.16, 295.2 ± 11.60, and 308.8 ± 4.32, respectively. The difference between the control group and the group treated with 100 ng/mL leptin was statistically significant (P < .05). CONCLUSIONS: Endothelial nitric oxide synthase expression in human umbilical vein endo- thelial cells increased depending on the leptin dose and the highest increase was in the group treated with 100 ng/mL leptin.

Anticancer activity of linalool: comparative investigation of ultrastructural changes and apoptosis in breast cancer cells.

Breast cancer is the most common cancer in women in the world. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Linalool is aromatic compounds from the monoterpene group. It is the main constituents of essential oils and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study was to investigate the antiproliferativeand apoptotic, effects of linalool in MCF-7 and MDA-MB-231 human breast cancer cells. MCF-7 and MDA-MB-231 human breast cancer cells were treated with different concentrations of linalool (100, 200, 400, 600, 800, 1000 µM) at 24 h and 48 h. MTT assay for cell proliferation and Annexin V assay for apoptosis was done. The morphology of breast cancer cells was investigated by light microscope and scanning electron microscope (SEM). The study show that linalool significantly induced apoptosis in all groups as dose and time-dependent (p < .05). Linalool has apoptotic and antiproliferative properties in a concentration and time-dependent manner in breast cancer cells. The cytotoxic effects of linalool on MCF-7 and MDA-MB-231 human breast cancer cells was found to be associated with apoptotic cell death. Linalool was more effective on MCF-7 human breast cancer cells in smaller amounts.

Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis.

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and antioxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (on the 30th day, single-dose 20 mg/ml, intraperitoneal), MSU + MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU + PINX and MSU + PINX + MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status) were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU + MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.

Treatment with crocin suppresses diabetic nephropathy progression via modulating TGF-ß1 and oxidative stress in an experimental model of pinealectomized diabetic rats.

One of the most common complications of diabetes is diabetic nephropathy (DN). Uncontrolled hyperglycemia leads to histopathologic alterations in the kidney that prevent normal renal function. This study aimed to explore the effects of crocin treatment via virtue of its numerous beneficial properties in streptozotocin-induced pinealectomized diabetic rats. The pinealectomy procedure was conducted on the first day of the study. On the 30th day following pinealectomy, streptozotocin (STZ) (50 mg/kg) was administered intraperitoneally in Wistar rats for induction of diabetes. Diabetes was confirmed on the 3rd day following STZ administration by determining the glucose levels. Daily crocin treatment intraperitoneally for 15 days (50 mg/kg) ameliorated impaired renal oxidant/antioxidant balance, reduced TGF-ß1 immuno-staining around tubules, and promoted improvement of renal architecture. Moreover, crocin administration improved altered renal function parameters, including serum Cr and BUN, and also increased creatinine clearance. In conclusion, the protective effects of crocin on diabetic nephropathy might be associated with its powerful antioxidant properties, its ability to improve tissue antioxidant status, and its ability to prevent inflammatory pathways.

Protective effects of quercetin against testis damage caused by cisplatin.

We investigated the effects of quercetin on cisplatin induced testicular toxicity using histopathological, immunohistochemical and biochemical methods. We used four groups of Wistar albino male: control, quercetin, cisplatin, cisplatin + quercetin. We measured tissue malondialdehyde (MDA) and catalase (CAT) biochemically. We assessed apoptosis as indicated by P63 immunoreactivity. Testis tissues of the control group exhibited normal histology. In the cisplatin group, the diameter of the seminiferous tubule and thickness of the germinal epithelium were decreased compared to the control group. In the cisplatin group, degeneration of the germinal epithelium, cell separation from the basal membrane, giant cell formation, cell loss, atrophy and vacuolization were observed in the seminiferous tubule. We found hyalinization around the seminiferous tubule, intertubule hyalinization and perivascular fibrosis. In the cisplatin + quercetin group, we found that quercetin decreased atrophy, giant cell formation and vacuolization significantly. We found that quercetin exhibited ameliorative effects following cisplatin induced testicular damage.

Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress.

The aim of the present study was to investigate the therapeutic and protective effects of linalool against doxorubicin (DOX)-induced kidney injury. Forty-eight Wistar rats were divided into 8 groups as follows; Control, DOX [20 mg/kg, intraperitoneal (ip) single dose DOX], linalool (LIN50 and LIN100; 50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively), DOX + LIN50 and DOX + LIN100 (20 mg/kg single dose of DOX via ip on first day and 50 mg/kg and 100 mg/kg linalool via ip, respectively), LIN50 + DOX and LIN100 + DOX (50 mg/kg and 100 mg/kg linalool via ip for 5 days, respectively and 20 mg/kg single dose of DOX via ip on fifth day). Doxorubicin led to a significant increase in the level of malondialdehyde (MDA) in the kidney, whereas superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels decreased remarkably when compared with control. On the other hand, LIN supplementation before and after DOX treatment led to a significant decrease in MDA and also increases in SOD, CAT and GSH levels. DOX caused significant increases in the levels of blood urea nitrogen (BUN) and creatinine (Cr) levels in the plasma, while LIN supplementation as a therapeutic and preventive agent led to significant decreases in BUN and Cr levels. The current study demonstrated that LIN supplementation after or before DOX treatment can led to therapeutic and preventive effects against DOX-induced renal damage.

Effects of pinealectomy and crocin treatment on rats with isoproterenol-induced myocardial infarction.

The present study aimed to analyze the effects of pinealectomy and crocin treatment in isoproterenol-induced myocardial damage. Seventy rats were divided into seven groups: control, sham control, pinealectomy (PNX), isoproterenol (ISO; 85 mg/kg on the 29th and 30th days of the experiment, subcutaneous injection), PNX + ISO, PNX + crocin (50 mg/kg/day for 30 days, intragastric administration), and PNX + ISO + crocin. PNX procedure was performed on the first day of the study. A significant increase was observed in serum cardiac damage markers (CK-MB, Troponin I) after ISO administration. ISO administration led to a significant increase in cardiac oxidative stress parameters, such as malondialdehyde (MDA) and total oxidant status (TOS), while it led to a decrease in antioxidant defense system parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) when compared to control groups. Elevated MDA and TOS levels were observed, while reduced SOD and CAT activities, and decreased GSH and TAS levels were observed in the group that underwent PNX and ISO administration when compared to the PNX group. Furthermore, in the PNX + ISO + Crocin group, SOD and CAT activities, and GSH and TAS levels ameliorated and MDA and TOS levels were reduced with the crocin treatment when compared to the PNX + ISO group. Also, marked increases were observed in serum cardiac markers, histopathological and immunohistochemical findings after the crocin treatment. All findings demonstrated that crocin could be employed as a cardioprotective agent due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats.

Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malignancies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. In the present study, we aimed to investigate the effects of crocin on doxorubicin-induced cardiotoxicity in rats. Forty rats were randomly divided into four groups: (a) control [received normal saline as a dose of 1 ml/kg by intraperitoneal injection (ip) for 15 days], (b) crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX+crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection, and crocin as a dose of 40 mg/kg/24h i.p for 15 days). As compared to the controls, the results showed that DOX administration caused significant increases in lipid indices [triglyseride (TG), low-dencity lipoproteins (LDL) (p<0.001), and very low-dencity lipoproteins (VLDL) (p<0.005)], oxidative stress parameters [malondialdehyde (MDA) and total oxidant status (TOS) (p<0.001)] and cardiac markers [creatine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI) (p<0.001)]. Besides, significant decreases in antioxidant defense systems [glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) (p<0.001)] were observed. The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile (p<0.005), cardiac markers (p<0.005), and oxidative stress indices (p<0.001) as compared to DOX group. Histopathologically, significant increase in the mean histopathological damage score (MHDS) was found in the DOX group as compared to the controls (p<0.001). In contrast, the administration of crocin with DOX alleviated MHDS in myocardium (p<0.001). Taken together, our results reveal that crocin might be a cardioprotective agent in DOX-treated patients for cancer.