Cytoprotective Agents
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Questions and Answers

What is the function of S-adenosyl methionine (SAMe) in the treatment of liver disease?

  • Increases hepatic glutathione and has anti-oxidant and anti-inflammatory properties (correct)
  • Converts prednisone to prednisolone
  • Suppresses TNFa, IL-1 and NFKB
  • Scavenges free radicals
  • What is the effect of ursodeoxycholic acid (ursodiol) on the immune system?

  • Suppresses IL-2 (correct)
  • Increases TNFa
  • Activates NFKB
  • Induces apoptosis
  • What is the function of vitamin E in the treatment of liver disease?

  • Antioxidant that protects phospholipids from injury (correct)
  • Antioxidant that increases hepatic glutathione
  • Immune system modulator that increases IL-2
  • Anti-inflammatory that suppresses TNFa
  • What is the effect of silymarin on cytochrome P450 activity in people?

    <p>Decreases it</p> Signup and view all the answers

    What is the function of glutathione in hepatocytes?

    <p>Antioxidant that reduces oxidative damage</p> Signup and view all the answers

    What is the effect of N-acetylcysteine (NAC) on hepatic cysteine and glutathione levels?

    <p>Replenishes them</p> Signup and view all the answers

    What breeds of dogs are commonly associated with chronic hepatitis?

    <p>Doberman and English Springer Spaniel</p> Signup and view all the answers

    Why is prednisolone preferred over prednisone in the treatment of severe liver disease in dogs?

    <p>Prednisone has to be converted to prednisolone in the liver</p> Signup and view all the answers

    What is the primary consideration for giving prednisolone in dogs with chronic hepatitis?

    <p>Moderate to severe hepatic inflammation on histological examination</p> Signup and view all the answers

    What is the typical dosage of prednisolone for dogs with chronic hepatitis?

    <p>1-2 mg/kg PO q 24 h</p> Signup and view all the answers

    What is the purpose of repeating liver biopsy 6 weeks after starting prednisolone treatment?

    <p>To assess the patient's response to treatment</p> Signup and view all the answers

    What is the mechanism of action of zinc in reducing copper absorption in dogs?

    <p>Zinc increases the synthesis of metallothionein by enterocytes</p> Signup and view all the answers

    What is the typical reference interval for hepatic copper concentration in healthy dogs?

    <p>1000 mcg/g</p> Signup and view all the answers

    What is the recommended duration of treatment for dogs with hepatic copper concentrations >1500 mcg/g?

    <p>At least 10 months</p> Signup and view all the answers

    What is the purpose of giving lactulose to patients with hepatic encephalopathy?

    <p>To reduce ammonia production in the gut</p> Signup and view all the answers

    What is a contraindication for protein restriction in cats?

    <p>High requirement for protein</p> Signup and view all the answers

    What is the recommended timing for measuring the copper concentration of a liver biopsy specimen after starting chelation therapy?

    <p>6 months after starting treatment</p> Signup and view all the answers

    What is the recommended dietary approach for dogs with hepatic copper accumulation?

    <p>Copper-restricted diet</p> Signup and view all the answers

    Study Notes

    Cytoprotective Agents

    • Liver is susceptible to oxidative damage
    • Glutathione is an essential antioxidant stored in hepatocytes, synthesized from L-glutamate, L-cysteine, and glycine
    • S-adenosyl methionine (SAMe) increases hepatic glutathione, has anti-oxidant and anti-inflammatory properties, and may be antiapoptotic and anti-carcinogenic
    • N-acetylcysteine (NAC) helps replenish hepatic cysteine and glutathione levels, used for treatment of acetaminophen toxicity
    • Silymarin scavenges free radicals, reduces lipid peroxidation, and may suppress TNFa, IL-1, and NFKB
    • Vitamin E protects phospholipids from injury
    • Ursodeoxycholic acid (ursodiol) has choleretic, cytoprotective, and immunomodulatory effects, including the suppression of IL-2

    Anti-inflammatory and Immunosuppressive Drugs

    • Prednisolone is used to treat dogs with severe liver disease, especially in cases of chronic hepatitis
    • Autoimmunity may be a common cause of chronic hepatitis in certain breeds (e.g., Doberman, English Springer Spaniel)
    • Prednisolone is often used to treat cats with lymphocytic cholangitis and chronic neutrophilic cholangitis
    • Azathioprine is a purine analog that can be used in dogs with chronic hepatitis
    • Cyclosporine is a T-cell inhibitor that has been used with some success in chronic hepatitis

    Medications for Treating Hepatic Copper Accumulation

    • D-penicillamine is a chelating agent that combines with copper, allowing it to be mobilized from the liver and excreted in the urine
    • Trientine is a chelating agent that causes increased urinary excretion of copper
    • Zinc decreases absorption of copper from the GI tract and induces increased synthesis of metallothionein
    • Copper accumulation is an important cause of chronic hepatitis in dogs, and sections of liver should be routinely stained for copper

    Hepatic Encephalopathy

    • Consider a commercial, lower protein diet
    • Protein restriction is contraindicated in cats due to high requirement
    • Lactulose is an osmotic laxative used to treat hepatic encephalopathy
    • Neomycin is a poorly absorbed aminoglycoside antibiotic used to treat hepatic encephalopathy
    • Metronidazole is used to treat hepatic encephalopathy

    Hepatic Fibrosis

    • There are no proven treatments for hepatic fibrosis
    • Chronic inflammation leads to activation of myofibroblasts, including hepatic stellate cells and portal fibroblasts
    • Treat underlying inflammation to prevent additional fibrosis
    • ARB losartan has shown promising antifibrotic effects in rats

    Ascites

    • Spironolactone is the diuretic of choice, as furosemide can lead to hypovolemia, hypokalemia, and hypochloremic alkalosis, which can precipitate HE

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    Description

    Learn about the agents that protect liver cells from damage, including glutathione, S-adenosyl methionine, N-acetylcysteine, and silymarin, and their properties in antioxidant and anti-inflammatory activities.

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