Effects of temperature on anoxic submergence: skeletal buffering, lactate distribution, and glycogen utilization in the turtle, Trachemys scripta

To test the hypothesis that submergence temperature affects the distribution of the lactate load and glycogen utilization during anoxia in turtles, we sampled a variety of tissues after 7 days, 24 h, and 4 h of anoxic submergence at 5, 15, and 25 degrees C, respectively. These anoxic durations were chosen because we found that they produced similar decreases in plasma HCO(3)(-) ( approximately 18-22 meq/l). The sampled tissues included ventricle, liver, small intestine, carapace, and the following muscles: flexor digitorum longus, retrahens capitis, iliofibularis, and pectoralis. Shell and skeleton sequestered 41.9, 34.1, and 26.1% of the estimated lactate load at 5, 15, and 25 degrees C. The changes in plasma Ca(2+) and Mg(2+), relative to the estimated lactate load, decreased with increased temperature, indicating greater buffer release from bone at colder temperatures. Tissue lactate contents, relative to plasma lactate, increased with the temperature of the submergence. Glucose mobilization and tissue glycogen utilization were more pronounced at 15 and 25 degrees C than at 5 degrees C. We conclude that, in slider turtles, the ability of the mineralized tissue to participate in the buffering of lactic acid during anoxia is inversely related to temperature, causing the lactate burden to shift to the tissues at warmer temperatures. Muscles utilize glycogen during anoxia more at warmer temperatures.     

Lactate metabolism in anoxic turtles: an integrative review

Painted turtles can accumulate lactic acid to extremely high concentrations during long-term anoxic submergence, with plasma lactate exceeding 200 mmol l⁻¹. The aims of this review are twofold: (1) To summarize aspects of lactate metabolism in anoxic turtles that have not been reviewed previously and (2) To identify gaps in our knowledge of turtle lactate metabolism by comparing it with lactate metabolism during and after exercise in other vertebrates. The topics reviewed include analyses of lactate’s fate during recovery, the effects of temperature on lactate accumulation and clearance, the interaction of activity and recovery metabolism, fuel utilization during recovery, stress hormone responses during and following anoxia, and cellular lactate transport mechanisms. An analysis of lactate metabolism in anoxic turtles in the context of the ‘lactate shuttle’ hypothesis is also presented.     

Lactic acid buffering by bone and shell in anoxic softshell and painted turtles

We tested two hypotheses: first, that the inferior anoxia tolerance of the softshell turtle, Apalone spinifera, compared to the western painted turtle, Chrysemys picta bellii, is related to its less mineralized shell, and second, that turtle bone, like its shell, stores lactate during prolonged anoxia. Lactate concentrations of blood, hindlimb bone, and shell were measured on normoxic Apalone and Chrysemys and after anoxic submergence at 10 degrees C for 2 and 9 d, respectively. Blood and shell concentrations of Ca(2+), Mg(2+), Na(+), K(+), and inorganic phosphate (P(i); for shell only) were also measured. Because a preliminary study indicated lactate distribution in Chrysemys throughout its skeleton during anoxia at 20 degrees C, we used hindlimb bones as representative skeletal samples. Apalone shell, though a similar percentage of body mass as Chrysemys shell, had higher water content (76.9% vs. 27.9%) and only 20%-25% as much Ca(2+), Mg(2+), CO(2), and P(i). When incubated at constant pH of 6.0 or 6.5, Apalone shell powder released only 25% as much buffer per gram wet weight as Chrysemys shell. In addition, plasma [Ca(2+)] and [Mg(2+)] increased less in Apalone during anoxia at an equivalent plasma lactate concentration. Lactate concentrations increased in the shell and skeletal bone in both species. Despite less mineralization, Apalone shell took up lactate comparably to Chrysemys. In conclusion, a weaker compensatory response to lactic acidosis in Apalone correlates with lower shell mineralization and buffer release and may partially account for the poorer anoxia tolerance of this species.     

Translational regulation in the anoxic turtle, <Emphasis Type="Italic">Trachemys scripta elegans</Emphasis>

Liver cancer is the sixth most common cancer worldwide and 3rd most common cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancer and is a major public health problem. Due to the advanced stages of HCC at the time of diagnosis, utilizing the conventional treatment for solid tumors frequently ends with treatment failure, recurrence, or poor survival. HCC is highly refractory to chemotherapy and other systemic treatments, and locoregional therapies or selective internal radiation therapies are largely palliative. Considering how the pathogenesis of HCC often induces an immunosuppressed state which is further amplified by post-treatment recurrence and reactivation, immunostimulation provides a potential novel approach for the treatment of HCC. Immune response(s) of the body may be potentiated by immunomodulation of various effector cells such as B-cells, T-cells, Treg cells, natural killer cells, dendritic cells, cytotoxic T-lymphocytes, and other antigen-presenting cells; cellular components such as genes and microRNA; and molecules such as proteins, proteoglycans, surface receptors, chemokines, and cytokines. Targeting these effectors individually has helped in the development of newer therapeutic approaches; however, combinational therapies targeting multi-faceted biomarkers have yielded better results. Still, there is a need for further research to develop novel therapeutic strategies which may act as either complementary or an alternative treatment to the standard therapy protocols of HCC. This review focuses on potential cellular and molecular targets, as well as the role of virotherapy and combinational therapy in the treatment of HCC.