A clinically relevant combination treatment with doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice.

BACKGROUND AND AIM: Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is not well understood whether a combination therapy of DOX and CPS can induce hepatotoxicity. We therefore sought to determine whether co-administration of DOX and CPS at their clinically relevant doses and frequency results in hepatotoxicity. METHODS: Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2mg /kg and CPS-50mg/kg once a week for 4 weeks. After the treatment period, liver histology and various serum biomarkers of hepatotoxicity were assessed. RESULTS: Co-treatment of DOX and CPS did not alter the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, albumin, globulin, or total protein. Similarly, co-administration of DOX and CPS did not result in a noticeable change in liver histology. However, it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase (AST). Elevated serum AST levels were also associated with increased serum creatinine kinase (CK) levels, suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and CPS. CONCLUSION: Taken together, our results, for the first time, suggest that co-administration of DOX and CPS, at their clinically relevant doses and frequency does not induce a significant hepatotoxicity in the mice.

Oroxylum indicum extract, at a physiologically relevant dosage, does not induce hepatotoxicity in C57BL/6J mice.

BACKGROUND: Botanical supplements have been proven to provide beneficial health effects. However, they can induce unintended adverse events such as hepatotoxicity. Oroxylum indicum extract (OIE, Sabroxy®) has several health benefits including anti-inflammatory, anti-arthritic, antifungal, antibacterial, and neuroprotective effects. It is currently unknown whether OIE has the potential to induce hepatotoxicity. PURPOSE: In the current study, we sought to determine whether OIE can induce hepatotoxicity in C57BL/6J mouse model. METHODS: The male mice were fed powdered rodent food (control group) or powdered rodent food mixed with OIE (Sabroxy®, 500mg/kg) daily for 4 weeks. Following the treatment, we assessed liver histology and serum levels of biomarkers commonly associated with liver damage, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). RESULTS: No significant alterations were observed in liver histology, and serum levels of ALT, AST, ALP, bilirubin, albumin, globulin and total protein in the OIE fed mice compared to the control mice. CONCLUSION: Taken together, our results suggest that OIE, when fed at its physiologically relevant dosage, does not induce hepatotoxicity in C57BL/6J mice.

Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment.

While chemotherapy is the most effective therapeutic approach for treating a variety of cancer patients, commonly used chemotherapeutic agents, often induce several adverse effects. Escalating evidence indicates that chemotherapeutics, particularly doxorubicin (DOX) and cyclophosphamide (CPS), induce cognitive impairment associated with central nervous system toxicity. This study was performed to determine neuroprotective effects of Oroxylum indicum extract (OIE) in regard to preventing chemotherapy induced cognitive impairment (CICI) occurring after 4 cycles of DOX (2mg/kg) and CPS (50mg/kg) combination chemotherapy in male C57BL/6J mice. OIE significantly prevented the chemotherapy impaired short-term cognitive performance, exploratory behavior associated with cognitive performance, cognitive performance, and spatial learning and memory in the Y-maze, Open-Field, Novel Object Recognition, and Morris Water Maze tests, respectively. These data suggest that OIE protects from the CICI. OIE decreased the reactive oxygen species and lipid peroxide generated by the chemotherapy treatment in the brain, while also blocking the chemotherapy-induced glutathione depletion. These results establish that OIE exhibits potent antioxidant activity in chemotherapy treated mice. Notably, OIE significantly increased the Complex-I and Complex-IV activities in the brain, indicating that OIE enhances mitochondrial function in the brain. In silico analysis of the major active chemical constituents (Oroxylin A, Baicalein and Chrysin) of OIE indicated that OIE has a favorable absorption, distribution, metabolism and excretion (ADME) profile. Taken together, our results are consistent with the conclusion that OIE prevents CICI by counteracting oxidative stress and perhaps by improving mitochondrial function.

Carbamoyl Functionalized Bent para-Phenylenes via an Unexpected Reaction of the Burgess Reagent with α-Ketols.

The attempted dehydration of macrocyclic α-ketols with the Burgess reagent has resulted in the unexpected synthesis of carbamoylated, bent para-phenylene units. The same reaction with an acyclic analogue affords the intended dehydration product, indicating that the change in reactivity is conformationally controlled and a result of the bifunctional nature of the Burgess reagent.

A Survey on the Impact of COVID-19 on Lacrimal Surgery: The Asia-Pacific Perspective.

AIM: To assess the impact of the COVID-19 pandemic-related lockdown on lacrimal surgery among oculoplastic surgeons in the Asia-Pacific region. METHODS: An institutional board review approved anonymous electronic survey was sent out via email to oculoplastic surgeons across the Asia-Pacific region. All responses were tabulated and analysed. RESULTS: A total of 259 valid responses were received. Nearly 87% of the surgeons agreed that lacrimal procedures were associated with a high risk of COVID-19 transmission. In all, at the time of taking the survey, 151/259 (58.3%) of the surgeons were not performing any lacrimal surgeries in view of the COVID-19 pandemic and 71/259 (27.4%) of the respondents were only performing emergency lacrimal surgeries. External dacryocystorhinostomy was the most commonly performed lacrimal procedure across the region and lacrimal procedures contributed to at least 25% of the income for nearly a third of the respondents. Majority of the respondents were female (52.9%), but a significantly higher proportion of male oculoplastic surgeons were still performing lacrimal surgeries during the lockdown. Over 75% of respondents indicated that resuming lacrimal procedures is important to their practice. CONCLUSION: The survey showed that there was a general agreement among the surveyed oculoplastic surgeons in the Asia-Pacific region that lacrimal procedures were associated with a high risk of COVID-19 transmission and over 85% of them of had either stopped performing elective lacrimal surgeries altogether or were providing only emergent care. It is likely that not performing elective lacrimal procedures, COVID-19 has financially impacted a high percentage of the surveyed oculoplastic surgeons.

Malignant melanoma of the rectum presenting as orbital metastasis.

An orbital mass being the presenting sign of disseminated systemic metastasis is a rare clinical picture. Here, the authors describe the case of a 52-year old Asian-Indian female who presented with unilateral proptosis and motility restriction. Imaging showed an irregular orbital mass infiltrating the right lateral rectus and with a significant intraconal component. Incisional biopsy helped to diagnose a malignant melanoma and exhaustive systemic imaging showed that the primary was found to be arising from the rectum. This represents the first reported case of malignant melanoma of the rectum metastasizing to the orbit and presenting with proptosis and reduced vision.

Predictable hematological markers associated with cognitive decline in valid rodent models of cognitive impairment.

Endogenous (hyperglycemia) and exogenous (therapeutic, prophylactic, street drugs) factors can considerably contribute to cognitive impairment (CI). Currently, there are few invasive and/or noninvasive markers that correlate with CI and those that do exist require expensive or invasive techniques to predict and accurately measure the cognitive decline. Therefore, we sought to determine hematological markers as predictors of CI in two different chemically induced valid rodent models of CI (streptozotocin induced hyperglycemic model and chemotherapy [doxorubicin/cyclophosphamide] treated rodent model). Hematological markers were analyzed in the above rodent models of CI CI and compared to their respective control groups. There was a significant increase in creatinine kinase, lactate dehydrogenase and aspartate aminotransferase (AST) in the chemotherapy group. Blood urea nitrogen (BUN), alkaline phosphatase (ALP), bilirubin, creatinine and glucose levels were significantly increased in the streptozotocin group. Interestingly, triglycerides were significantly elevated in both the streptozotocin and chemotherapy groups. Previous studies with human subjects have shown a potential link between the increase in triglyceride levels and CI. Likewise, our data indicate a notable correlation with an increase in triglycerides to cognitive impairment in the rodent models. This suggests elevated levels of triglycerides could prove to be a potential noninvasive hematological marker for the increased risk of CI. Further studies are warranted to determine the causal relationship between elevated triglyceride levels and CI.