{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/30821"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/30821","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"The effect of mTOR inhibitor rapamycin on a dietary Drosophila melanogaster model of calcium oxalate nephrolithiasis","abstract":"Impaired cellular tolerance of reactive oxygen species (ROS) has been suggested as a common mechanistic link associated with aging in both metabolic syndrome and nephrolithiasis. The mechanistic (mammalian) target of rapamycin (mTOR) activity is characteristic of metabolic syndrome. When nutrients are abundant, mTOR is active. Conversely, fasting inhibits mTOR. Metabolic syndrome is correlated with an increased risk of self-reported or imaging findings of nephrolithiasis. At the individual level, patients with a higher BMI have an increased prevalence of recurrent symptomatic nephrolithiasis, 24-hour urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH. Calcium oxalate crystals produce ROS in renal epithelial cells and upregulate ROS and also mTOR activity. Rapamycin pharmacologically inhibits mTOR leading to autophagy – a natural defense mechanism against ROS – and drives sub-cellular recycling machinery to a net catabolic state. Ideally, inhibiting mTOR limits the duration and degree of damage done by ROS and subsequent inflammatory process. Additionally, improved clearance of damaged organelles prevents runaway generation of ROS by mitochondrial dysfunction associated with calcium oxalate crystal adherence and internalization. Taken together, this may prevent the progression of calcium oxalate urolithiasis. In this study, we examined the effect of short-term intermittent rapamycin treatment on the area of calcium oxalate concretion in the Malpighian tubules of a Drosophila melanogaster fed a lithogenic diet containing 0.1% sodium oxalate.","abstract_html":"Impaired cellular tolerance of reactive oxygen species (ROS) has been suggested as a common mechanistic link associated with aging in both metabolic syndrome and nephrolithiasis. The mechanistic (mammalian) target of rapamycin (mTOR) activity is characteristic of metabolic syndrome. When nutrients are abundant, mTOR is active. Conversely, fasting inhibits mTOR. Metabolic syndrome is correlated with an increased risk of self-reported or imaging findings of nephrolithiasis. At the individual level, patients with a higher BMI have an increased prevalence of recurrent symptomatic nephrolithiasis, 24-hour urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH. Calcium oxalate crystals produce ROS in renal epithelial cells and upregulate ROS and also mTOR activity. Rapamycin pharmacologically inhibits mTOR leading to autophagy – a natural defense mechanism against ROS – and drives sub-cellular recycling machinery to a net catabolic state. Ideally, inhibiting mTOR limits the duration and degree of damage done by ROS and subsequent inflammatory process. Additionally, improved clearance of damaged organelles prevents runaway generation of ROS by mitochondrial dysfunction associated with calcium oxalate crystal adherence and internalization. Taken together, this may prevent the progression of calcium oxalate urolithiasis. In this study, we examined the effect of short-term intermittent rapamycin treatment on the area of calcium oxalate concretion in the Malpighian tubules of a Drosophila melanogaster fed a lithogenic diet containing 0.1% sodium oxalate.","abstract_has_math":false,"creators":["Pignanelli, Michael T"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Surgery","degree_department":null,"school":null,"contributors":[],"advisors":["Razvi, Hassan","Jennifer Bjazevic"],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-11-18","date_published":"2020-11-18","updated_at":"2026-07-27T21:56:03Z","subjects":["nephrolithiasis","rapamycin","mTOR","Drosophila melanogaster","calcium oxalate","sodium oxalate","Malpighian tubule","aging","metabolic syndrome","reactive oxygen species","autophagy."],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/30821","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Razvi, Hassan","Jennifer Bjazevic"]},{"key":"dc:creator","label":"Author","values":["Pignanelli, Michael T"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T18:45:58Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T18:45:58Z"]},{"key":"dc:date.issued","label":"Date","values":["2020-11-18"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Surgery"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["nephrolithiasis","rapamycin","mTOR","Drosophila melanogaster","calcium oxalate","sodium oxalate","Malpighian tubule","aging","metabolic syndrome","reactive oxygen species","autophagy."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/30821"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Impaired cellular tolerance of reactive oxygen species (ROS) has been suggested as a common mechanistic link associated with aging in both metabolic syndrome and nephrolithiasis. The mechanistic (mammalian) target of rapamycin (mTOR) activity is characteristic of metabolic syndrome. When nutrients are abundant, mTOR is active. Conversely, fasting inhibits mTOR. Metabolic syndrome is correlated with an increased risk of self-reported or imaging findings of nephrolithiasis. At the individual level, patients with a higher BMI have an increased prevalence of recurrent symptomatic nephrolithiasis, 24-hour urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH. Calcium oxalate crystals produce ROS in renal epithelial cells and upregulate ROS and also mTOR activity. Rapamycin pharmacologically inhibits mTOR leading to autophagy – a natural defense mechanism against ROS – and drives sub-cellular recycling machinery to a net catabolic state. Ideally, inhibiting mTOR limits the duration and degree of damage done by ROS and subsequent inflammatory process. Additionally, improved clearance of damaged organelles prevents runaway generation of ROS by mitochondrial dysfunction associated with calcium oxalate crystal adherence and internalization. Taken together, this may prevent the progression of calcium oxalate urolithiasis. In this study, we examined the effect of short-term intermittent rapamycin treatment on the area of calcium oxalate concretion in the Malpighian tubules of a Drosophila melanogaster fed a lithogenic diet containing 0.1% sodium oxalate."]},{"key":"dc:title","label":"Title","values":["The effect of mTOR inhibitor rapamycin on a dietary Drosophila melanogaster model of calcium oxalate nephrolithiasis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Razvi, Hassan","Jennifer Bjazevic"],"dc:creator":["Pignanelli, Michael T"],"dc:date.accessioned":["2025-07-10T18:45:58Z"],"dc:date.available":["2025-07-10T18:45:58Z"],"dc:date.issued":["2020-11-18"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["Impaired cellular tolerance of reactive oxygen species (ROS) has been suggested as a common mechanistic link associated with aging in both metabolic syndrome and nephrolithiasis. The mechanistic (mammalian) target of rapamycin (mTOR) activity is characteristic of metabolic syndrome. When nutrients are abundant, mTOR is active. Conversely, fasting inhibits mTOR. Metabolic syndrome is correlated with an increased risk of self-reported or imaging findings of nephrolithiasis. At the individual level, patients with a higher BMI have an increased prevalence of recurrent symptomatic nephrolithiasis, 24-hour urinary excretion of oxalate, sodium, uric acid, calcium, and phosphorous as well as lower pH. Calcium oxalate crystals produce ROS in renal epithelial cells and upregulate ROS and also mTOR activity. Rapamycin pharmacologically inhibits mTOR leading to autophagy – a natural defense mechanism against ROS – and drives sub-cellular recycling machinery to a net catabolic state. Ideally, inhibiting mTOR limits the duration and degree of damage done by ROS and subsequent inflammatory process. Additionally, improved clearance of damaged organelles prevents runaway generation of ROS by mitochondrial dysfunction associated with calcium oxalate crystal adherence and internalization. Taken together, this may prevent the progression of calcium oxalate urolithiasis. In this study, we examined the effect of short-term intermittent rapamycin treatment on the area of calcium oxalate concretion in the Malpighian tubules of a Drosophila melanogaster fed a lithogenic diet containing 0.1% sodium oxalate."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/30821"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["nephrolithiasis","rapamycin","mTOR","Drosophila melanogaster","calcium oxalate","sodium oxalate","Malpighian tubule","aging","metabolic syndrome","reactive oxygen species","autophagy."],"dc:title":["The effect of mTOR inhibitor rapamycin on a dietary Drosophila melanogaster model of calcium oxalate nephrolithiasis"],"dc:type":["thesis"],"thesis:degree_discipline":["Surgery"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:03Z"}